bluuebunny/crossref_metadata_2025 huggingface dataset:
ChemInform Abstract: A New Efficient Synthetic Method for 3‐Iodothyronamine and Its Potent Hypothermic Efficacy.
Authors: Kim Joong‐Gon , Song Young‐Kyu , Jeon Su‐Yeon , Lim Ye‐Ji , Ju Hyunwoo , Choi Inho , Chung Chan‐Moon
Published: February 2012

Compared to the conventional method the title synthesis has the advantage of less synthetic steps and higher overall yield.
ChemInform Abstract: Two‐Dimensional Dielectric Nanosheets: Novel Nanoelectronics from Nanocrystal Building Blocks
Authors: Osada Minoru , Sasaki Takayoshi
Published: February 2012

Review: 183 refs.
ChemInform Abstract: Shvo′s Catalyst in Hydrogen Transfer Reactions
Authors: Warner Madeleine C. , Casey Charles P. , Baeckvall Jan‐E.
Published: February 2012

Review: 94 refs.
ChemInform Abstract: Bond Activation by Metal—Ligand Cooperation: Design of Green Catalytic Reactions Based on Aromatization—Dearomatization of Pincer Complexes
Authors: Gunanathan Chidambaram , Milstein David
Published: February 2012

Review: 93 refs.
ChemInform Abstract: Bifunctional Transition Metal Based Molecular Catalysts for Asymmetric Syntheses
Authors: Ikariya Takao
Published: February 2012

Review: 80 refs.
ChemInform Abstract: Developments in Transition‐Metal‐Catalyzed Reactions Using Electrophilic Nitrogen Sources
Authors: Barker Timothy J. , Jarvo Elizabeth R.
Published: February 2012

Review: ca. 70 refs.
ChemInform Abstract: Recent Advances in Selective Reactions Promoted by Barium Reagents
Authors: Yanagisawa Akira , Yoshida Kazuhiro
Published: February 2012

Review: about 50 refs.
ChemInform Abstract: Microwave Assisted Phosphorus Organic Chemistry: A Review
Authors: Guenin E. , Meziane D.
Published: February 2012

Review: 122 refs.
ChemInform Abstract: Blood‐Brain Barrier Transport of Opioid Analgesics
Authors: Suzuki Toyofumi
Published: February 2012

Review: 47 refs.
ChemInform Abstract: ECHO Probes: A Concept of Fluorescence Controll for Practical Nucleic Acid Sensing
Authors: Okamoto Akimitsu
Published: February 2012

Review: 144 refs.
Modeling and Simulation of Evaporating Spray Flows with Coalescence in an Eulerian Framework
Authors: Gopireddy Srikanth R. , Humza Rana M. , Gutheil Eva
Published: February 2012

The study concerns the modeling and simulation of gas‐droplet and droplet‐droplet interactions on spray dynamics and droplet size distribution in turbulent spray flows where the spray is described in an Eulerian framework. The primary focus is to develop a suitable mathematical model that can describe the underlying physics including the polydispersion of the spray, evaporation, drag, coalescence, and interaction with the convective gas flow. This is achieved by applying the direct quadrature method of moments, which is extended to account for evaporation, drag force and coalescence by implementing well‐established standard models available in literature. The model is developed and formulated in three‐dimensional physical space, whereas the computations are carried out in a one‐dimensional geometric configuration since the reference experimental setup is only one‐dimensional. A water spray carried by nitrogen was injected through a hollow cone nozzle into a cylindrical spray chamber. The results reveal that evaporation and coalescence have a significant effect on the droplet size distribution whereas the droplet velocity is influenced by drag force as anticipated. Computational and experimental results agree very well when coalescence is considered.
Removal of Arsenic from Simulated Groundwater Using GAC‐Ca in Batch Reactor: Kinetics and Equilibrium Studies
Authors: Mondal Prasenjit , Mohanty Bikash , Majumder Chandrajit Balo
Published: February 2012

This paper deals with kinetics and equilibrium studies on the adsorption of arsenic species from simulated groundwater containing arsenic (As(III)/As(V), 1:1), Fe, and Mn in concentrations of 0.188, 2.8, and 0.6 mg/L, respectively, by Ca2+ impregnated granular activated charcoal (GAC‐Ca). Effects of agitation period and initial arsenic concentration on the removal of arsenic species have also been described. Although, most of the arsenic species are adsorbed within 10 h of agitation, equilibrium reaches after ∼24 h. Amongst various kinetic models investigated, the pseudo second order model is more adequate to explain the adsorption kinetics and film diffusion is found to be the rate controlling step for the adsorption of arsenic species on GAC‐Ca. Freundlich isotherm is adequate to explain the adsorption equilibrium. However, empirical polynomial isotherm gives more accurate prediction on equilibrium specific uptakes of arsenic species. Maximum specific uptake (qmax) for the adsorption of As(T) as obtained from Langmuir isotherm is 135 µg/g.
Fine structural organization of the hemiellipsoid body of the land hermit crab, Coenobita clypeatus
Authors: Brown Sheena , Wolff Gabriella
Published: February 2012

Electron microscopical observations of the hemiellipsoid bodies of the land hermit crab Coenobita clypeatus resolve microglomerular synaptic complexes that are comparable to those observed in the calyces of insect mushroom bodies and which characterize olfactory inputs onto intrinsic neurons. In an adult hermit crab, intrinsic neurons and one class of efferent neurons originate from neuronal somata of globuli cells covering the hemiellipsoid bodies. Counts of their nucleoli show that about 120,000 globuli cells supply each hemiellipsoid body in an adult hermit crab. This number is comparable to the number of globuli cells supplying mushroom bodies of certain insects, such as honey bees and cockroaches. Counts of axons in tracts leading from the olfactory lobes to the hemiellipsoid bodies resolve 20,000 afferent axons, however, an order of magnitude greater than known for any insect. These afferent axons provide numerous swollen varicosities, each presynaptic to many small profiles, and thus comparable to the microglomeruli that characterize insect mushroom body calyces. Also, common to mushroom bodies and hemiellipsoid bodies are arrangements of intrinsic neurons, afferent neurons containing dense core vesicles, and systems of serial synaptic complexes that relate to postsynaptic profiles of efferent neurons. Together, the ultrastructural organization of the hemiellipsoid bodies of C. clypeatus supports the proposition that this center may share a common origin with the insect mushroom body despite obvious divergent evolution of overall shape. J. Comp. Neurol. 520:2847–2863, 2012. © 2012 Wiley Periodicals, Inc.
A DFT Study of the Structures of Aux Clusters on a CeO2(111) Surface
Authors: Teng Bo‐Tao , Wu Feng‐Min , Huang Wei‐Xin , Wen Xiao‐Dong , Zhao Lei‐Hong , Luo Meng‐Fei
Published: February 2012

Studying the structures of metal clusters on oxide supports is challenging due to their various structural possibilities. In the present work, a simple rule in which the number of Au atoms in different layers of Aux clusters is changed successively is used to systematically investigate the structures of Aux (x=1–10) clusters on stoichiometric and partially reduced CeO2(111) surface by DFT calculations. The calculations indicate that the adsorption energy of a single Au atom on the surface, the surface structure, as well as the AuAu bond strength and arrangement play the key roles in determining Aux structures on CeO2(111). The most stable Au2 and Au3 clusters on CeO2(111) are 2D vertical structures, while the most stable structures of Aux clusters (x>3) are generally 3D structures, except for Au7. The 3D structures of large Aux clusters in which the Au number in the bottom layer does not exceed that in the top layer are not stable. The differences between Aux on CeO2(111) and Mg(100) were also studied. The stabilizing effect of surface oxygen vacancies on Aux cluster structures depends on the size of Aux cluster and the relative positions of Aux cluster and oxygen vacancy. The present work will be helpful in improving the understanding of metal cluster structures on oxide supports.
Tuning the Properties of Redox‐Active Guanidino‐Functionalized Aromatic Ligands by Substitution: Experiment and Theory
Authors: Peters Anastasia , Herrmann Hendrik , Magg Martin , Kaifer Elisabeth , Himmel Hans‐Jörg
Published: February 2012

Substitution of the aromatic hydrogen atoms in the electron donors 1,2,4,5‐tetrakis(tetramethylguanidino)benzene (1a) and 1,2,4,5‐tetrakis(N,N′‐dimethyl‐N,N′‐ethyleneguanidino)benzene (1b) by iodide (to give 2a and 2b) and nitro groups (to give 3a and 3b) afforded new redox‐active ligands. Their properties (electron donor capacity, Brønsted basicity and optical spectra) have been analyzed and compared with the unsubstituted 1,2,4,5‐tetrakis(guanidino)benzenes. The experimental results are supplemented by quantum chemical calculations. The first late‐transition metal complex of the push–pull ligand 3a was prepared and characterized and its oxidation studied.
Stoichiometry of the MexA‐OprM binding, as investigated by blue native gel electrophoresis
Authors: Ferrandez Yann , Monlezun Laura , Phan Gilles , Benabdelhak Houssain , Benas Philippe , Ulryck Nathalie , Falson Pierre , Ducruix Arnaud , Picard Martin , Broutin Isabelle
Published: February 2012

Multidrug resistance has become a serious concern in the treatment of bacterial infections. A prominent role is ascribed to the active efflux of xenobiotics out of the bacteria by a tripartite protein machinery. The mechanism of drug extrusion is rather well understood, thanks to the X‐ray structures obtained for the Escherichia coli TolC/AcrA/AcrB model system and the related Pseudomonas aeruginosa OprM/MexA/MexB. However, many questions remain unresolved, in particular the stoichiometry of the efflux pump assembly. On the basis of blue native polyacrylamide gel electrophoresis (BN‐PAGE) (Wittig et al., Nat. Protoc. 2006, 1, 418–428), we analyzed the binding stoichiometry of both palmitylated and non‐palmitylated MexA with the cognate partner OprM trimer at different ratios and detergent conditions. We found that β‐octyl glucopyranoside (β‐OG) detergent was not suitable for this technique. Then we proved that MexA has to be palmitylated in order to stabilized the complex formation with OprM. Finally, we provided evidence for a two by two (2, 4, 6, or upper) binding of palmitylated MexA per trimer of OprM.
Designing of sequencing assay assisted by capillary electrophoresis based on DNA folding analysis: An application to the VCAM1 gene
Authors: Arcadu Bastiana , Orrù Marco , Piga Rosaria , Orrù Germano
Published: February 2012

In this work, we describe a fast standardized molecular method for DNA sequencing assisted by capillary electrophoresis with a particular emphasis on bioinformatic approaches to avoid sequencing errors due to complex DNA regions. In this case, the method was applied on the human vascular adhesion molecule 1 (VCAM1) gene. VCAM1 sequence, in fact, shows many thermodynamically critical parameters such as very low GC content (30–40%), many nucleotide stack areas, i.e. hairpins, self‐complementary regions. With a traditional primer design approach it was difficult to design correct PCR oligonucleotides, thus sometimes, the chromatogram showed an illegible profile. By a strategy involving various bioinformatic tools (Mfold, Oligo, Highter), we investigated the role of the DNA‐folding analysis in the assistance of primer design for the DNA sequencing of fragments with high −ΔG stem‐loop regions. This new approach allowed us to sequence nine different VCAM1 regions each containing the respective exon. Our results, based on different DNA samples recruited from oral brushes taken from ten different subjects, identified four different SNPs (c.662–7C/T, c.1793–79A>G, c.2079C/T, c.2208A>G) with high reproducibility.
A new view to intracellular pathogens and host responses in the South of Spain
Authors: Portillo Francisco García‐del , Cossart Pascale
Published: February 2012

A workshop on ‘The Biology of Intracellular Bacterial Pathogens’ was held last October in a venue of the International University of Andalusia (UNIA) located in the World Historic Heritage town of Baeza, in the South of Spain. This Workshop gathered leading scientists from around the world to discuss their latest findings related to the mechanisms that intracellular pathogens use to subvert and manipulate host cell functions. The workshop focused on novel aspects that imprint current research in this discipline, including the heterogeneous behaviour of the pathogen at the population level, the host determinants that modulate susceptibility to the infection, the search for new drugs to combat these particular types of infections and also cutting edge technologies based on new imaging approaches and the use of microfluidics. Discussion on these topics provided new insights into the biology of these pathogens and enriched the field with new ideas for understanding why colonization of the intracellular niche of eukaryotic cells is a preferred strategy used by important human pathogens.
An efficient approach for frequency‐domain and time‐domain hydrodynamic analysis of dam–reservoir systems
Authors: Lin Gao , Wang Yi , Hu Zhiqiang
Published: February 2012

An efficient procedure is developed for the hydrodynamic analysis of dam–reservoir systems. The governing equations of hydrodynamic pressure in the frequency as well as time domain are derived in the framework of the scaled boundary finite element method. The water compressibility and absorption of reservoir sediments can be conveniently taken into consideration. By extending the reservoir to infinity with uniform cross‐section, only the dam–reservoir interface needs to be discretized to model the fluid domain, and the hydrodynamic pressure in the stream direction is solved analytically. Several numerical examples including a gravity dam with an inclined upstream face and an arch dam with a reservoir of arbitrary cross‐section are provided to demonstrate the computational efficiency and accuracy of the proposed method. Copyright © 2012 John Wiley & Sons, Ltd.
Asymmetric addition of a nitrogen nucleophile to an enoate in the presence of a chiral phase‐transfer catalyst: A novel approach toward enantiomerically enriched protected β‐amino acids
Authors: Weiß Markus , Borchert Sonja , Rémond Emmanuelle , Jugé Sylvain , Gröger Harald
Published: February 2012

A proof of concept for the asymmetric organocatalytic aza‐Michael addition reaction of nitrogen nucleophiles with simple and readily available alkyl enoates as acceptor molecules in the presence of a chiral phase‐transfer catalyst has been demonstrated. The desired enantiomerically enriched β‐amino acid derivatives were obtained in up to 86% yield and with enantioselectivities of up to 37% ee. © 2012 Wiley Periodicals, Inc. Heteroatom Chem 23:202–209, 2012; View this article online at wileyonlinelibrary.com. DOI 10.1002/hc.21004
Medullary thyroid carcinoma and 2q37 deletion in a patient with nevoid basal cell carcinoma syndrome: Clinical description and genetic analysis
Authors: Coca–Pelaz Andrés , Llorente–Pendás Jose Luis , García–Martínez Jorge , Vivanco–Allende Blanca , Balbín Milagros , Suárez Carlos , Hermsen Mario
Published: February 2012

Background

Nevoid basal cell carcinoma syndrome (NBCCS) is a rare, inheritable, multisystem disorder characterized by numerous basal cell carcinomas (BCCs), maxillary keratocyst, and musculoskeletal malformations. Occasionally, it is associated with malignancies like rhabdomyoma, melanoma, and sinonasal undifferentiated carcinoma, to name a few.

Methods

A patient presented with NBCCS with a medullary thyroid carcinoma. Clinical, surgical details, and germline genetic analysis are herein described.

Results

A 32‐year‐old woman was referred to our department with suspicion of medullary thyroid carcinoma, which was confirmed by histopathological examination. The patient was diagnosed as also having NBCCS. Germline mutation analysis indicated wild‐type genes PTCH1 and RET. DNA copy number analysis by high resolution microarray comparative genomic hybridization (CGH) revealed a small interstitial loss at chromosomal band 2q37.3.

Conclusion

To our knowledge, this is the first described patient with NBCCS carrying a medullary thyroid carcinoma and a 2q37 deletion, which confirms that this syndrome can be associated with many different malignancies. © 2012 Wiley Periodicals, Inc. Head Neck, 2013
Voice outcomes after concurrent chemoradiotherapy for advanced nonlaryngeal head and neck cancer: A prospective study
Authors: Paleri Vinidh , Carding Paul , Chatterjee Sanjoy , Kelly Charles , Wilson Janet Ann , Welch Andrew , Drinnan Michael
Published: February 2012

Background

The voice impact of treatment for nonlaryngeal head and neck primary sites remains unknown.

Methods

We conducted a prospective study of a consecutive sample of patients undergoing chemoradiation for nonlaryngeal head and neck cancer. The Voice Symptom Scale (VoiSS) was completed, and voice recordings were made at 3 time‐points.

Results

Of 42 recruited patients, 34 completed the measures before and in the early posttreatment phase (mean 16.5 weeks), while 21 patients were assessed at the final time‐point (mean, 20.4 months). VoiSS scores showed statistically significant progressive deterioration in the total score (p = .02) and impairment subscale (p < .0001) through to the final assessment. Acoustic measures and perceptual ratings deteriorated significantly (p < .001) in the early posttreatment weeks and improved at the final assessment, but not to the baseline. Interrater agreement was excellent for expert measures.

Conclusion

To the best of our knowledge, this is the first prospective study to show that chemoradiation therapy for nonlaryngeal head and neck cancer has a significant effect on the patients' self‐reported voice quality, even in the long term. © 2012 Wiley Periodicals, Inc. Head Neck, 2012
Fibronectin is essential for survival but is dispensable for proliferation of hepatocytes in acute liver injury in mice
Authors: Moriya Kei , Sakai Keiko , Yan Michel H. , Sakai Takao
Published: February 2012

Acute liver injury causes massive hepatocyte apoptosis and/or fatal liver damage. Fibronectin, an extracellular matrix glycoprotein, is prominently expressed during adult tissue repair. However, the extent of fibronectin dependence on hepatocyte response to acute liver damage remains to be defined. Because identification of hepatic survival factors is critical for successful therapeutic intervention in liver failure, this relationship has been investigated using a fibronectin-deficient mouse model of acute liver injury. Here, we show that lack of fibronectin induces significantly increased hepatocyte apoptosis, which is accompanied by significant down-regulation of the antiapoptotic protein, B-cell lymphoma—extra large (Bcl-xL). Furthermore, fibronectin deficiency leads to a significantly elevated production of hepatocyte growth factor in hepatic stellate cells postinjury, which, in turn, results in an earlier onset and acceleration of hepatocyte regeneration. Primary hepatocytes on fibronectin are protected from reactive oxygen species–induced cellular damage, retaining the expression of Bcl-xL, whereas those on type I collagen are not. This retained expression of Bcl-xL is inhibited by the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. Conclusion: We provide evidence that fibronectin-mediated matrix survival signals for hepatocytes are transduced through the PI3K/Bcl-xL-signaling axis in response to injury. This work defines fibronectin as a novel antiapoptotic factor for hepatocytes after acute liver injury, but demonstrates that fibronectin is not essential for subsequent hepatocyte proliferation. (HEPATOLOGY 2012;56:311–321)
Hepatitis C virus selectively perturbs the distal cholesterol synthesis pathway in a genotype-specific manner
Authors: Clark Paul J. , Thompson Alexander J. , Vock David M. , Kratz Lisa E. , Tolun Adviye A. , Muir Andrew J. , McHutchison John G. , Subramanian Mani , Millington David M. , Kelley Richard I. , Patel Keyur
Published: February 2012

Hepatitis C virus (HCV) subverts host cholesterol metabolism for key processes in its lifecycle. How this interference results in the frequently observed, genotype-dependent clinical sequelae of hypocholesterolemia, hepatic steatosis, and insulin resistance (IR) remains incompletely understood. Hypocholesterolemia typically resolves after sustained viral response (SVR), implicating viral interference in host lipid metabolism. Using a targeted cholesterol metabolomic platform we evaluated paired HCV genotype 2 (G2) and G3 patient sera for changes in in vivo HCV sterol pathway metabolites. We compared HCV genotypic differences in baseline metabolites and following antiviral treatment to assess whether sterol perturbation resolved after HCV eradication. We linked these metabolites to IR and urine oxidative stress markers. In paired sera from HCV G2 (n = 13) and G3 (n = 20) patients, baseline sterol levels were lower in G3 than G2 for distal metabolites (7-dehyrocholesterol (7DHC) 0.017 versus 0.023 mg/dL; P
adj = 0.0524, cholesterol 140.9 versus 178.7 mg/dL; P
adj = 0.0242) but not the proximal metabolite lanosterol. In HCV G3, SVR resulted in increased levels of distal metabolites (cholesterol [Δ55.2 mg/dL; P
adj = 0.0015], 7DHC [Δ0.0075 mg/dL; P
adj = 0.0026], lathosterol [Δ0.0430 mg/dL P
adj = 0.0405]). In contrast, lanosterol was unchanged after SVR (P = 0.9515). Conclusion: HCV G3, but not G2, selectively interferes with the late cholesterol synthesis pathway, evidenced by lower distal sterol metabolites and preserved lanosterol levels. This distal interference resolves with SVR. Normal lanosterol levels provide a signal for the continued proteolysis of 3-hydroxyl-3-methylglutaryl coenzyme A reductase, which may undermine other host responses to increase cholesterol synthesis. These data may provide a hypothesis to explain why hypocholesterolemia persists in chronic HCV infection, particularly in HCV G3, and is not overcome by host cholesterol compensatory mechanisms. (HEPATOLOGY 2012;56:49–56)
Role of transcriptional and posttranscriptional regulation of methionine adenosyltransferases in liver cancer progression
Authors: Frau Maddalena , Tomasi Maria L. , Simile Maria M. , Demartis Maria I. , Salis Fabiana , Latte Gavinella , Calvisi Diego F. , Seddaiu Maria A. , Daino Lucia , Feo Claudio F. , Brozzetti Stefania , Solinas Giuliana , Yamashita Satoshi , Ushijima Toshikazu , Feo Francesco , Pascale Rosa M.
Published: February 2012

Down-regulation of the liver-specific MAT1A gene, encoding S-adenosylmethionine (SAM) synthesizing isozymes MATI/III, and up-regulation of widely expressed MAT2A, encoding MATII isozyme, known as MAT1A:MAT2A switch, occurs in hepatocellular carcinoma (HCC). Here we found Mat1A:Mat2A switch and low SAM levels, associated with CpG hypermethylation and histone H4 deacetylation of Mat1A promoter, and prevalent CpG hypomethylation and histone H4 acetylation in Mat2A promoter of fast-growing HCC of F344 rats, genetically susceptible to hepatocarcinogenesis. In HCC of genetically resistant BN rats, very low changes in the Mat1A:Mat2A ratio, CpG methylation, and histone H4 acetylation occurred. The highest MAT1A promoter hypermethylation and MAT2A promoter hypomethylation occurred in human HCC with poorer prognosis. Furthermore, levels of AUF1 protein, which destabilizes MAT1A messenger RNA (mRNA), Mat1A-AUF1 ribonucleoprotein, HuR protein, which stabilizes MAT2A mRNA, and Mat2A-HuR ribonucleoprotein sharply increased in F344 and human HCC, and underwent low/no increase in BN HCC. In human HCC, Mat1A:MAT2A expression and MATI/III:MATII activity ratios correlated negatively with cell proliferation and genomic instability, and positively with apoptosis and DNA methylation. Noticeably, the MATI/III:MATII ratio strongly predicted patient survival length. Forced MAT1A overexpression in HepG2 and HuH7 cells led to a rise in the SAM level, decreased cell proliferation, increased apoptosis, down-regulation of Cyclin D1, E2F1, IKK, NF-κB, and antiapoptotic BCL2 and XIAP genes, and up-regulation of BAX and BAK proapoptotic genes. In conclusion, we found for the first time a post-transcriptional regulation of MAT1A and MAT2A by AUF1 and HuR in HCC. Low MATI/III:MATII ratio is a prognostic marker that contributes to determine a phenotype susceptible to HCC and patients' survival. Conclusion: Interference with cell cycle progression and I-kappa B kinase (IKK)/nuclear factor kappa B (NF-κB) signaling contributes to the antiproliferative and proapoptotic effect of high SAM levels in HCC. (HEPATOLOGY 2012;56:165–175)
Peroxisome proliferator-activated receptor alpha induction of uncoupling protein 2 protects against acetaminophen-induced liver toxicity
Authors: Patterson Andrew D. , Shah Yatrik M. , Matsubara Tsutomu , Krausz Kristopher W. , Gonzalez Frank J.
Published: February 2012

Acetaminophen (APAP) overdose causes acute liver failure in humans and rodents due in part to the destruction of mitochondria as a result of increased oxidative stress followed by hepatocellular necrosis. Activation of the peroxisome proliferator-activated receptor alpha (PPARα), a member of the nuclear receptor superfamily that controls the expression of genes encoding peroxisomal and mitochondrial fatty acid β-oxidation enzymes, with the experimental ligand Wy-14,643 or the clinically used fibrate drug fenofibrate, fully protects mice from APAP-induced hepatotoxicity. PPARα-humanized mice were also protected, whereas Ppara-null mice were not, thus indicating that the protection extends to human PPARα and is PPARα-dependent. This protection is due in part to induction of the PPARα target gene encoding mitochondrial uncoupling protein 2 (UCP2). Forced overexpression of UCP2 protected wildtype mice against APAP-induced hepatotoxicity in the absence of PPARα activation. Ucp2-null mice, however, were sensitive to APAP-induced hepatotoxicity despite activation of PPARα with Wy-14,643. Protection against hepatotoxicity by UCP2-induction through activation of PPARα is associated with decreased APAP-induced c-jun and c-fos expression, decreased phosphorylation of JNK and c-jun, lower mitochondrial H2O2 levels, increased mitochondrial glutathione in liver, and decreased levels of circulating fatty acyl-carnitines. These studies indicate that the PPARα target gene UCP2 protects against elevated reactive oxygen species generated during drug-induced hepatotoxicity and suggest that induction of UCP2 may also be a general mechanism for protection of mitochondria during fatty acid β-oxidation. (HEPATOLOGY 2012;56:281–290)
Small‐molecule screen identifies modulators of EWS/FLI1 target gene expression and cell survival in Ewing's sarcoma
Authors: Boro Aleksandar , Prêtre Kathya , Rechfeld Florian , Thalhammer Verena , Oesch Susanne , Wachtel Marco , Schäfer Beat W. , Niggli Felix K.
Published: February 2012

Ewing's sarcoma family of tumors (EFT) is characterized by the presence of chromosomal translocations leading to the expression of oncogenic transcription factors such as, in the majority of cases, EWS/FLI1. Because of its key role in Ewing's sarcoma development and maintenance, EWS/FLI1 represents an attractive therapeutic target. Here, we characterize PHLDA1 as a novel direct target gene whose expression is repressed by EWS/FLI1. Using this gene and additional specific well‐characterized target genes such as NROB1, NKX2.2 and CAV1, all activated by EWS/FLI1, as a read‐out system, we screened a small‐molecule compound library enriched for FDA‐approved drugs that modulated the expression of EWS/FLI1 target genes. Among a hit‐list of nine well‐known drugs such as camptothecin, fenretinide, etoposide and doxorubicin, we also identified the kinase inhibitor midostaurin (PKC412). Subsequent experiments demonstrated that midostaurin is able to induce apoptosis in a panel of six Ewing's sarcoma cell lines in vitro and can significantly suppress xenograft tumor growth in vivo. These results suggest that midostaurin might be a novel drug that is active against Ewing's cells, which might act by modulating the expression of EWS/FLI1 target genes.
Cytotoxicity of new duplex drugs linking 3′‐C‐ethynylcytidine and 5‐fluor‐2′‐deoxyuridine against human melanoma cells
Authors: Schott Sarah , Niessner Heike , Sinnberg Tobias , Venturelli Sascha , Berger Alexander , Ikenberg Kristian , Villanueva Jessie , Meier Friedegund , Garbe Claus , Busch Christian
Published: February 2012

Melanoma is an increasingly common and potentially fatal malignancy of the skin and some mucous membranes. As no cure exists for metastatic disease, there is an urgent need for novel drugs. 2′‐Deoxy‐5‐fluorouridylyl‐(3′‐5′)‐3′‐C‐ethynylcytidine [5‐FdU(3′‐5′)ECyd] and 3′‐C‐ethynylcytidinylyl‐(5′→1‐O)‐2‐O‐octadecyl‐sn‐glycerylyl‐(3‐O→5′)‐2′‐deoxy‐5‐fluorouridine [ECyd‐lipid‐5‐FdU] represent cytostatic active duplex drugs, which can be metabolized into various active antimetabolites. We evaluated the cytotoxicity of these heterodinucleoside phosphate analogs, their corresponding monomers ECyd and 5‐FdU and combinations thereof on six metastatic melanoma cell lines and six ex vivo patient‐derived melanoma cells in comparison to current standard cytostatic agents and the BRAF V600E inhibitor Vemurafenib. In vitro (real‐time)‐proliferation assays demonstrated that 5‐FdU(3′‐5′)ECyd and ECyd‐lipid‐5‐FdU had a high cytotoxic efficacy causing 75% melanoma cell death at concentrations in the nanomolar and micromolar range. Cytotoxicity was conducted by induction of DNA cleavage indicating apoptotic cells. Chicken embryotoxicity demonstrated that the duplex drugs were less toxic than 5‐FdU at 0.01 μM. In vivo the duplex drug 5‐FdU(3′‐5′)ECyd was efficacious in the murine LOX IMVI melanoma xenograph model on administration of 11.2 mg/kg/injection every fourth day. Both duplex drugs are promising novel cytostatic agents for the treatment of malignant melanoma meriting clinical evaluation.
What proportion of lung cancer in never‐smokers can be attributed to known risk factors?
Authors: Sisti Julia , Boffetta Paolo
Published: February 2012

Though tobacco smoking is the primary risk factor for lung cancer, a significant fraction of lung cancer deaths occur in lifetime nonsmokers. In this article, we calculate the burden of lung cancer in never‐smokers attributable to previously identified risk factors in North America, Europe and China, using population‐based estimates of exposure prevalence and estimates of relative risk derived from recently published meta‐analyses. Population attributable fractions (PAFs) for individual risk factors ranged from 0.40 to 19.93%. Because of differences in the prevalence of exposures, the PAFs associated with several of the risk factors varied greatly by geographical region. Exposure to the selected risk factors appeared to explain a much larger proportion of lung cancer cases in never‐smokers in China than in Europe and North America. Our results demonstrate the geographic variability of the epidemiology of lung cancer in never‐smokers and highlight the need for further research in this area, particularly in Europe and North America.
Lipid peroxidation and DNA adduct formation in lymphocytes of premenopausal women: Role of estrogen metabolites and fatty acid intake
Authors: Sun Xin , Nair Jagadeesan , Linseisen Jakob , Owen Robert W. , Bartsch Helmut
Published: February 2012

A diet high in linoleic acid (an ω‐6 PUFA) increased the formation of miscoding etheno (ε) ‐ DNA adducts in WBC‐DNA of women, but not in men (Nair et al., Cancer Epidemiol Biomark Prev 1997;6:597‐601). This gender specificity could result from an interaction between ω‐6 PUFA intake and estrogen catabolism, via redox‐cycling of 4‐hydroxyestradiol (4‐OH‐E2) and subsequent lipid peroxidation (LPO). In this study, we investigated whether in premenopausal women LPO‐derived adducts in WBC‐DNA are affected by serum concentration of 2‐ and 4‐hydroxyestradiol metabolites and by fatty acid intake. DNA extracted from buffy coat and plasma samples, both blindly coded from healthy women (N = 124, median age 40 year) participating in the EPIC‐Heidelberg cohort study were analyzed. Three LPO‐derived exocyclic DNA adducts, εdA, εdC and M1dG were quantified by immuno‐enriched 32P‐postlabelling and estradiol metabolites by ultra‐sensitive GC‐mass spectrometry. Mean M1dG levels in WBC‐DNA were distinctly higher than those of εdA and εdC, and all were positively and significantly interrelated. Serum levels of 4‐OH‐E2, but not of 2‐OH‐E2, metabolites were positively related to etheno DNA adduct formation. Positive correlations existed between M1dG levels and linoleic acid intake or the ratios of dietary linoleic acid/oleic acid and PUFA/MUFA. Aerobic incubation of 4‐OH‐E2, arachidonic acid and calf thymus DNA yielded two to threefold higher etheno DNA adduct levels when compared with assays containing 2‐OH‐E2 instead. In conclusion, this study is the first to compare M1dG and etheno‐DNA adducts and serum estradiol metabolites in human samples in the same subjects. Our results support a novel mechanistic link between estradiol catabolism, dietary ω‐6 fatty acid intake and LPO‐induced DNA damage supported by an in vitro model. Similar studies in human breast epithelial tissue and on amplification of DNA‐damage in breast cancer patients are in progress.
Human papillomavirus types in 115,789 HPV‐positive women: A meta‐analysis from cervical infection to cancer
Authors: Guan Peng , Howell‐Jones Rebecca , Li Ni , Bruni Laia , de Sanjosé Silvia , Franceschi Silvia , Clifford Gary M.
Published: February 2012

Genotyping may improve risk stratification of high‐risk (HR) human papillomavirus (HPV)‐positive women in cervical screening programs; however, prospective data comparing the natural history and carcinogenic potential of individual HR types remain limited. A meta‐analysis of cross‐sectional HR HPV‐type distribution in 115,789 HPV‐positive women was performed, including 33,154 normal cytology, 6,810 atypical squamous cells of undetermined significance (ASCUS), 13,480 low‐grade squamous intraepithelial lesions (LSIL) and 6,616 high‐grade SIL (HSIL) diagnosed cytologically, 8,106 cervical intraepithelial neoplasia grade 1 (CIN1), 4,068 CIN2 and 10,753 CIN3 diagnosed histologically and 36,374 invasive cervical cancers (ICCs) from 423 PCR‐based studies worldwide. No strong differences in HPV‐type distribution were apparent between normal cytology, ASCUS, LSIL or CIN1. However, HPV16 positivity increased steeply from normal/ASCUS/LSIL/CIN1 (20–28%), through CIN2/HSIL (40/47%) to CIN3/ICC (58/63%). HPV16, 18 and 45 accounted for a greater or equal proportion of HPV infections in ICC compared to normal cytology (ICC:normal ratios = 3.07, 1.87 and 1.10, respectively) and to CIN3 (ICC:CIN3 ratios = 1.08, 2.11 and 1.47, respectively). Other HR types accounted for important proportions of HPV‐positive CIN2 and CIN3, but their contribution dropped in ICC, with ICC:normal ratios ranging from 0.94 for HPV33 down to 0.16 for HPV51. ICC:normal ratios were particularly high for HPV45 in Africa (1.85) and South/Central America (1.79) and for HPV58 in Eastern Asia (1.36). ASCUS and LSIL appear proxies of HPV infection rather than cancer precursors, and even CIN3 is not entirely representative of the types causing ICC. HPV16 in particular, but also HPV18 and 45, warrant special attention in HPV‐based screening programs.
Bone tissue engineering using bone marrow stromal cells and an injectable sodium alginate/gelatin scaffold
Authors: Xia Yang , Mei Fang , Duan Yongli , Gao Ying , Xiong Zhuo , Zhang Ting , Zhang Hongquan
Published: February 2012

To investigate the potential application of bone marrow stromal cells (BMSCs) and an injectable sodium alginate/gelatin scaffold for bone tissue engineering (BTE). The phenotype of osteogenic BMSCs was examined by mineralized nodules formation and type I collagen expression. Cell proliferation was evaluated by MTT assay. The biocompatibility of scaffold and osteogenic cells were examined by hematoxylin and eosin (H&E) staining. Ectopic bone formation as well as closure of rabbit calvarial critical‐sized defects following scaffold‐cell implantation were analyzed by histological examination and computed tomography (CT) scanning. Spindle‐shaped osteogenic cells of high purity were derived from BMSCs. The osteogenic cells and sodium alginate/gelatin (2:3) scaffold presented fine biocompatibility following cross‐linking with 0.6% of CaCl2. After implantation, the scaffold‐cell construct promoted both ectopic bone formation and bone healing in the rabbit calvarial critical‐sized defect model. Our data demonstrated that the sodium alginate/gelatin scaffold could be a suitable biomaterial for bone engineering, and the scaffold‐osteogenic cells construct is a promising alternative approach for the bone healing process. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2012.
Porous crosslinked poly(ε‐caprolactone fumarate)/nanohydroxyapatite composites for bone tissue engineering
Authors: Farokhi M. , Sharifi S. , Shafieyan Y. , Bagher Z. , Mottaghitalab F. , Hatampoor A. , Imani M. , Shokrgozar M.A.
Published: February 2012

Porous nanocomposites based on poly(ε‐caprolactone fumarate) (PCLF) resin matrix; N‐vinyl pyrrolidone (NVP) as a reactive diluents and nanohydroxyapatite (nHA) filler were developed for bone tissue engineering applications. Nanocomposite scaffolds with three different contents of nHA [5, 10, and 20 (w/w %)] were prepared by thermal crosslinking of PCLF followed by particulate leaching and characterized in terms of mechanical properties (cyclic loading) and in vitro cell‐material interaction by MTT assay and alkaline phosphatase activity measurements. Five osteoblastic cell lines were used to investigate the ability of the nanocomposites to support cell attachment, spreading, and proliferation after 3, 7, and 14 days. By adding the nHA filler phase, elastic modulus of the nanocomposites increased significantly. Scaffolds showed comparable biocompatibility to neat nHA particles, commercial bone graft (Bio‐Oss) and tissue culture polystyrene as control groups. According to the results it can be concluded that these scaffolds are potential candidates for bone substitution because of their mechanical strength and bioactivity. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2012.
Collagen scaffolds derived from fresh water fish origin and their biocompatibility
Authors: Pati Falguni , Datta Pallab , Adhikari Basudam , Dhara Santanu , Ghosh Kuntal , Mohapatra Pradeep Kumar Das
Published: February 2012

Collagen, a major component of native extracellular matrix, has diverse biomedical applications. However, its application is limited due to lack of cost‐effective production and risk of disease transmission from bovine sources currently utilized. This study describes fabrication and characterization of nano/micro fibrous scaffolds utilizing collagen extracted from fresh water fish origin. This is the first time collagen extracted from fresh water fish origin was studied for their biocompatibility and immunogenicity. The nano/micro fibrous collagen scaffolds were fabricated through self‐assembly owing to its amphiphilic nature and were subsequently cross‐linked.In vitrodegradation study revealed higher stability of the cross‐linked scaffolds with only ∼50% reduction of mass in 30 days, while the uncross‐linked one degraded completely in 4 days. Further, minimal inflammatory response was observed when collagen solution was injected in mice with or without adjuvant, without significant dilution of sera. The fish collagen scaffolds exhibited considerable cell viability and were comparable with that of bovine collagen. SEM and fluorescence microscopic analysis revealed significant proliferation rate of cells on the scaffolds and within 5 days the cells were fully confluent. These findings indicated that fish collagen scaffolds derived from fresh water origin were highly biocompatible in nature. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2012.
Tonicity enhancer binding protein (TonEBP) and hypoxia-inducible factor (HIF) coordinate heat shock protein 70 (Hsp70) expression in hypoxic nucleus pulposus cells: Role of Hsp70 in HIF-1α degradation
Authors: Gogate Shilpa S , Fujita Nobuyuki , Skubutyte Renata , Shapiro Irving M , Risbud Makarand V
Published: February 2012

The objective of our study was to examine the regulation of hypoxic expression of heat shock protein 70 (Hsp70) in nucleus pulposus cells and to determine if Hsp70 promoted hypoxia-inducible factor (HIF)-1α degradation. Rat nucleus pulposus cells were maintained in culture in either 21% or 1% oxygen. To determine the regulation of Hsp70 expression by tonicity enhancer binding protein (TonEBP) and HIF-1/2, loss-of-function and gain-of-function experiments and mutational analysis of the Hsp70 promoter were performed. Hypoxia increased Hsp70 expression in nucleus pulposus cells. Noteworthy, hypoxia increased TonEBP transactivation and mutation of TonE motifs blocked hypoxic induction of the Hsp70 promoter. In contrast, mutation of hypoxia response element (HRE) motifs coupled with loss-of-function experiments suggested that HIF-1 and HIF-2 suppressed Hsp70 promoter activity and transcription. Interestingly, HIF-α interferes with TonEBP function and suppresses the inductive effect of TonEBP on the Hsp70 promoter. In terms of Hsp70 function, when treated with Hsp70 transcriptional inhibitor, KNK437, there was an increase in HIF-1α protein stability and transcriptional activity. Likewise, when Hsp70 was overexpressed, the stability of HIF-1α and its transcriptional activity decreased. Hsp70 interacted with HIF-1α under hypoxic conditions and evidenced increased binding when treated with MG132, a proteasomal inhibitor. These results suggest that Hsp70 may promote HIF-1α degradation through the proteasomal pathway in nucleus pulposus cells. In hypoxic and hyperosmolar nucleus pulposus cells, Hsp70, TonEBP, and HIFs form a regulatory loop. We propose that the positive regulation by TonEBP and negative regulation of Hsp70 by HIF-1 and HIF-2 may serve to maintain Hsp70 levels in these cells, whereas Hsp70 may function in controlling HIF-1α homeostasis. © 2012 American Society for Bone and Mineral Research.
A two‐step synthesis of deuterium labeled 8, 8, 9, 9‐d4‐hexadecane from nonanoic acid
Authors: Zhou Lei , Bian Xinyu , Yang Shizhong , Mu Bozhong
Published: February 2012

Labeled compounds are essential in elucidating metabolic mechanisms and reaction pathways. A two‐step synthesis of deuterium‐labeled 8, 8, 9, 9‐d4‐hexadecane from nonanoic acid is described here. The synthesis procedures involved hydrogen–deuterium exchange of nonanoic acid with 3.00 m DCl‐D2O and then Kolbe electrolysis of the deuterated nonanoic acid to achieve the desired n‐alkane that was confirmed by gas chromatography‐mass spectrometry and 1H nuclear magnetic resonance. This method might provide an alternative route for the preparation of specifically deuterated alkanes of different chain lengths (C > 4) in which deuterium atoms are located at two adjacent carbons of the alkane's carbon chain. Copyright © 2012 John Wiley & Sons, Ltd.
Influence of forest structure on density and nest success of mature forest birds in managed landscapes
Authors: Bakermans Marja H. , Rodewald Amanda D. , Vitz Andrew C.
Published: February 2012

Managing for forest wildlife requires attention not only to quantity but quality of forests within the landscape. We examined the extent to which local structural attributes and landscape context of forest stands explained variation in density and reproductive success of mature forest birds across 12 sites in southeast Ohio, USA, 2004–2006. Results suggest that several structural characteristics influenced bird–habitat relationships in our study. Densities of 3 songbird species (i.e., ovenbird [Seiurus aurocapilla], cerulean warbler [Setophaga cerulea], and scarlet tanager [Piranga olivacea]) were positively related to canopy openness, which is usually a function of canopy gaps. Habitat attributes described by ground litter, understory density, and canopy height were positively associated with densities of ground (i.e., worm‐eating warbler [Helmitheros vermivorum]), or shrub nesting species (i.e., Kentucky and hooded warblers [Geothlypis formosaandSetophaga citrina], respectively). Furthermore, the number of small trees likely drove the positive relationship between density of wood thrush (Hylocichla mustelina), a subcanopy nester. After accounting for temporal variability in daily nest survival rates, the odds of nest survival for all species increased 10.5% for every 1% increase in canopy openness and decreased 1.4% for each 5% increase in understory vegetation density. Habitat–nest survival relationships were not apparent at the level of the individual species. Our results suggest that structural attributes produced by increasing habitat heterogeneity may be necessary for conservation of forest bird communities. © 2012 The Wildlife Society.
Tunable photonic delay lines in optical fibers
Authors: Chin S. , Thévenaz L.
Published: February 2012

A comprehensive overview is presented about optical fiber‐based tunable photonic delay lines, which have been steadily developed over the last decade for the realization of all‐optically controlled timing functions. The most widely used techniques, such as those based on slow & fast light and wavelength conversion associated to dispersion, are described and their physical limitations are discussed in terms of the maximal achievable delay, the associated signal distortion and signal bandwidth. Besides, an entirely different approach for all‐optical signal delaying is introduced. This technique is based on movable grating reflectors dynamically generated in highly birefringent optical fibers. This type of delay line has experimentally demonstrated large tunable delaying with a moderate signal distortion for high capacity optical data streams and even for wideband analog signals.
Two‐Component In situ Forming Supramolecular Hydrogels as Advanced Biomaterials in Vitreous Body Surgery
Authors: Böhm Indra , Strotmann Falko , Koopmans Carsten , Wolf Isabel , Galla Hans‐Joachim , Ritter Helmut
Published: February 2012

Polymeric β‐CD and poly{(2‐acrylamido‐2‐methyl‐1‐propanesulfonic acid sodium salt)‐co‐[6‐(acrylamido)‐N‐adamantylhexaneamide]} are synthesized to build in situ forming hydrogels based on host/guest interactions, so called physical hydrogels. The use of these hydrogels as a potential vitreous body substitute is discussed and recommended. Potential changes in cell morphology and cell vitality of the retinal ganglion cell line RGC‐5 are determined. DSC experiments with artificial membrane structures are performed. The analyses show that β‐CD overrides the harmful effects of the highly toxic adamantyl‐modified polymer. Although the final hydrogel is considered to be biocompatible, the application as a biomaterial has to be reconsidered.

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Schur–Weyl Theory for C*‐algebras
Authors: Beltiţă Daniel , Neeb Karl‐Hermann
Published: February 2012

To each irreducible infinite dimensional representation of a C*‐algebra , we associate a collection of irreducible norm‐continuous unitary representations of its unitary group , whose equivalence classes are parameterized by highest weights in the same way as the irreducible bounded unitary representations of the group are. These are precisely the representations arising in the decomposition of the tensor products under . We show that these representations can be realized by sections of holomorphic line bundles over homogeneous Kähler manifolds on which acts transitively and that the corresponding norm‐closed momentum sets distinguish inequivalent representations of this type.