bluuebunny/crossref_metadata_2025 huggingface dataset:
Stand der Technik von Polymer‐Elektrolyt‐Membran‐Brennstoffzellen – ein Überblick
Authors: Heinzel A.
Published: May 2009

Wenn regenerativ erzeugter Strom, biogene Energieträger und Wasserstoff die fossilen Energieträger nach und nach ablösen, ist eine der wichtigsten Zukunftstechnologien die effiziente Wandlung von Wasserstoff in elektrische Energie und Wärme. Mittlerweile sind in verschiedensten Anwendungen Polymer‐Elektrolyt‐Membran (PEM)‐Brennstoffzellensysteme in der Erprobung. Dank gezielter und kontinuierlicher staatlicher Förderung kann es gelingen, diese neue umweltfreundliche Technologie auch in Konkurrenz zu existierenden Techniken im Markt zu etablieren. Die Arbeit gibt einen Überblick über die Entwicklung der Brennstoffzellentechnologie.
Metabolomics, Metabonomics and Metabolite Profiling. Edited by William J. Griffiths.
Authors: Britz‐McKibbin Philip
Published: May 2009

RSC, Cambridge 2008 xi+324 pp., hardcover £ 89.00.—ISBN 978‐0‐85404‐299‐9
Cover Picture: Discovery of Riociguat (BAY 63‐2521): A Potent, Oral Stimulator of Soluble Guanylate Cyclase for the Treatment of Pulmonary Hypertension (ChemMedChem 5/2009)
Authors: Mittendorf Joachim , Weigand Stefan , Alonso‐Alija Cristina , Bischoff Erwin , Feurer Achim , Gerisch Michael , Kern Armin , Knorr Andreas , Lang Dieter , Muenter Klaus , Radtke Martin , Schirok Hartmut , Schlemmer Karl‐Heinz , Stahl Elke , Straub Alexander , Wunder Frank , Stasch Johannes‐Peter
Published: May 2009

The cover picture shows a schematic representation of soluble guanylate cyclase (sGC). This key signal‐transduction enzyme is typically found as a heterodimer, consisting of a larger α‐subunit and a smaller haeme‐binding β‐subunit. It is activated by the ubiquitous messenger nitric oxide and catalyzes the conversion of guanosine‐5′‐triphosphate (GTP) into the second messenger cyclic guanosine‐3′,5′‐monophosphate (cGMP). The depicted compound is riociguat, which was identified as a potent, oral sGC stimulator and is currently being investigated in phase III clinical trials for the treatment of pulmonary hypertension. For more details, see the Full Paper by J. Mittendorf et al. on p. 853 ff.

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Inside Cover: Homology Model Adjustment and Ligand Screening with a Pseudoreceptor of the Human Histamine H4 Receptor (ChemMedChem 5/2009)
Authors: Tanrikulu Yusuf , Proschak Ewgenij , Werner Tim , Geppert Tim , Todoroff Nickolay , Klenner Alexander , Kottke Tim , Sander Kerstin , Schneider Erich , Seifert Roland , Stark Holger , Clark Timothy , Schneider Gisbert
Published: May 2009

The inside cover picture shows the predicted histamine H4 receptor (H4R) binding pocket showing the conformation that best fits a H4R pseudoreceptor. Potential ligand–receptor interactions are shown as spheres, where the sphere size correlates with their computed relative importance: H‐bond acceptor (red) and donor (blue), and aromatic (green) pseudoatoms. Combining MD studies with pseudoreceptor matching yields preferred ligand binding sites in GPCR models. For details, see the Full Paper by G. Schneider et al. on p. 820 ff.

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Cover Picture: Local Modulation of the Redox State of p‐Nitrothiophenol Self‐Assembled Monolayers Using the Direct Mode of Scanning Electrochemical Microscopy (ChemPhysChem 7/2009)
Authors: Schwamborn Stefanie , Stoica Leonard , Neugebauer Sebastian , Reda Torsten , Schmidt Hanns‐Ludwig , Schuhmann Wolfgang
Published: May 2009

The cover picture illustrates the principle of molecular writing using direct‐mode scanning electrochemical microscopy (SECM). The redox state of the end groups of a p‐nitrothiophenol self‐assembled monolayer (SAM) is selectively reduced either to the hydroxylamine/nitoso redox couple or to the amino group. Besides the writing procedure, W. Schuhmann et al. demonstrate on p. 1066 that SECM can also be utilized for visualization or reading of the generated microstructure in feedback mode using hexacyanoferrate as redox mediator.

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Cre/lox recombination in the lower urinary tract
Authors: Wang Yinqiu , Tripathi Piyush , Guo Qiusha , Coussens Matthew , Ma Liang , Chen Feng
Published: May 2009

Tbx18 is a T‐Box transcription factor that has specific expression and indispensible function in the lower urinary tract. Here, we report the generation and characterization of a bacterial artificial chromosome (BAC) transgene expressing Cre under the control of Tbx18 regulatory elements. When crossed to the ROSA26R‐lacZ reporter mice, the Tbx18‐Cre transgene mediates loxP recombination in the mesenchymal derivatives in the lower urinary tract, especially in the smooth muscle cells (SMCs) and the stromal cells. There is no expression of this transgene in the urothelium or in the kidney. This Tbx18‐Cre transgene recapitulates the endogenous Tbx18 expression in the urinary system and can be used for the study of the development, physiology, and diseases in the urinary tract. Its additional expression in the epicardium, limb, vibrissae, and other structures would be useful for studies in the relevant fields. genesis 47:409–413, 2009. © 2009 Wiley‐Liss, Inc.
Synthesis and Characterization of Semiconductive Dichloridobis(thianthrene)gold(1+) Tetrachloridoaurate(1–)
Authors: Tjahjanto Rachmat Triandi , Beck Johannes
Published: May 2009

A new (thianthrene)gold(III) complex has been synthesized in liquid SO2 as the solvent from thianthrene (TA) andAuCl3. [AuCl2(TA)2][AuCl4] [triclinic, P$\bar {1}$, a = 9.9832(2) Å, b = 10.3404(2) Å, c = 15.0798(4) Å, α = 75.038(1)°, β = 81.610(1)°, γ = 68.409(1)°, V = 1396.15(5) Å3, Z = 2] has a salt‐like structure consisting of [AuCl2(TA)2]+ and [AuCl4]– ions, both with square‐planar coordinated gold atoms of oxidation state +3. In the cation, two bent TA molecules are coordinated to Au each through one sulfur atom. The title compound is thermally stable up to 425 K and is semiconducting with a conductivity reaching 25 mSm–1 at 380 K and a low activation energy of 0.43 eV. A model for the charge transport along the stacked cationic complexes is discussed. When dissolved in chloroform [AuCl2(TA)2][AuCl4] is converted into the already known uncharged, mononuclear complex [AuCl3(TA)], which shows that a polymerization isomerism exists between the two forms.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Five‐Membered Cyclic Nitronates in C–C Coupling with 1‐(tert‐Butyldimethylsilyloxy)‐1‐methoxyethylene
Authors: Smirnov Vladimir O. , Sidorenkov Alexander S. , Khomutova Yulia A. , Ioffe Sema L. , Tartakovsky Vladimir A.
Published: May 2009

Five‐membered cyclic nitronates 3 undergo TBSOTf‐catalysed C–C coupling reactions with silyl ketene acetal 4 to give good to excellent yields of 3,3‐disubstituted N‐(OTBS)‐isoxazolidines 5, which could not be obtained by previously known procedures. The problems of diastereoselectivity of the C–C coupling reactions are discussed. The transformations of the nitroso acetals 5 upon action of AcFOH/methanol or some reducing agents (H2/NiRa, LAH, Al/Hg) have been examined.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Evaluation of 6‐APA as a New Organocatalyst for a Direct Cross‐Aldol Reaction
Authors: Emer Enrico , Galletti Paola , Giacomini Daria
Published: May 2009

6‐Aminopenicillanic acid (6‐APA) and two of its derivatives, 6‐APA benzyl ester (6‐APA‐OBn) and Penicillin G (PenG), have been evaluated as catalysts for use in direct cross‐aldol reactions in different solvents and mixtures. The effects of catalyst loading, reaction time, pH and temperature on the yield and stereoselectivity have been studied. 6‐APA proved to be an effective catalyst in terms of yield for the reaction between cyclohexanone and p‐nitrobenzaldehyde, especially in neat conditions. The stereoselectivity of the reaction was conditioned by the presence of two competing mechanisms: one an imine–enamine pathway and the other a Brønsted acid catalysis. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Phosphane‐Free Palladium‐Catalyzed Carbonylative Suzuki Coupling Reaction of Aryl and Heteroaryl Iodides
Authors: Tambade Pawan J. , Patil Yogesh P. , Panda Anil G. , Bhanage Bhalchandra M.
Published: May 2009

The carbonylative cross‐coupling reaction of an arylboronic acid with an aryl iodide and a heteroaryl iodide to give unsymmetrical biaryl ketones was carried out by using Pd(tmhd)2/Pd(OAc)2 as a phosphane‐free catalyst. Various aryl and heteroaryl iodides with different arylboronic acid derivatives provided good to excellent yields of the desired products under optimized reaction conditions.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Detection of C Reactive Protein (CRP) in Serum by an Electrochemical Aptamer‐Based Sandwich Assay
Authors: Centi Sonia , Bonel Sanmartin Laura , Tombelli Sara , Palchetti Ilaria , Mascini Marco
Published: May 2009

A disposable electrochemical assay involving magnetic particles and carbon‐based screen‐printed electrodes (SPCEs) was developed for the detection of C Reactive Protein (CRP). CRP is a plasma protein and is among the most expressed proteins in acute phase inflammation cases, being a known biomarker for inflammatory states. The assay was based on a sandwich format in which a RNA aptamer was coupled to a monoclonal antibody and alkaline phosphatase (AP) was used as enzymatic label. After the sandwich assay, the modified magnetic beads were captured by a magnet on the surface of a graphite working electrode and the electrochemical detection was thus achieved through the addition of the AP substrate (α‐naphthyl‐phosphate) and α‐naphthol produced during the enzymatic reaction was detected using differential pulse voltammetry (DPV). The parameters influencing the different steps of the assay were optimized in order to reach the best sensitivity and specificity. With the optimized conditions, the assay was applied to the analysis of CRP free serum and serum samples.
Aptamer‐Based Electrochemical Sensor for Label‐Free Recognition and Detection of Cancer Cells
Authors: Pan Chunfeng , Guo Manli , Nie Zhou , Xiao Xilin , Yao Shouzhuo
Published: May 2009

An electrochemical biosensor was developed for the label‐free and selective detection of leukemia cells based on aptamer‐modified gold electrode using electrochemical impedance spectroscopy (EIS) technique. The thiol‐terminated aptamer (sgc8c) selected for CCRF‐CEM acute leukemia cells was self‐assembled onto the gold electrode surface as recognition probe, which was characterized by cyclic voltammetry (CV) and EIS using Fe(CN)63−/4− as a redox probe. The surface density of aptamers was determined by chronocoulometric method using a redox cation of Ru(NH3)63+. Upon incubation of the aptamer‐modified electrode with CCRF‐CEM cells, the electron‐transfer resistance (Ret) of Fe(CN)63−/4− on the sensor surface increased substantially. Only a small Ret change of the sensor to the control negative cell line RAJI was observed, indicating the excellent selectivity of the sensor. The selective capture of CCRF‐CEM cells on the sensor surface was also confirmed by fluorescence microscopy. A linear relationship between Ret and the logarithmic value of CCRF‐CEM cells concentration was found in the range of 1×104 to 1×107 cells/mL, with a detection limit of 6×103 cells/mL. This work provided a simple, convenient, low‐cost and label‐free method for early leukemia diagnosis.
Upregulation of plakophilin‐2 and its acquisition to adherens junctions identifies a novel molecular ensemble of cell–cell‐attachment characteristic for transformed mesenchymal cells
Authors: Rickelt Steffen , Winter‐Simanowski Stefanie , Noffz Edeltraut , Kuhn Caecilia , Franke Werner Wilhelm
Published: May 2009

In contrast to the desmosome‐containing epithelial and carcinoma cells, normal and malignantly transformed cells derived from mesenchymal tissues and tumors are connected only by adherens junctions (AJs) containing N‐cadherins and/or cadherin‐11, anchored in a cytoplasmic plaque assembled by α‐ and β‐catenin, plakoglobin, proteins p120 and p0071. Here, we report that the AJs of many malignantly transformed cell lines are characterized by the additional presence of plakophilin‐2 (Pkp2), a protein hitherto known only as a major component of desmosomal plaques, i.e., AJs of epithelia and carcinomatous cells. This massive acquisition of Pkp2 and its integration into AJ plaques of a large number of transformed cell lines is demonstrated with biochemical and immunolocalization techniques. Upregulation of Pkp2 and its integration into AJs has also been noted in some soft tissue tumors insitu and some highly proliferative colonies of cultured mesenchymal stem cells. As Pkp2 has recently been identified as a functionally important major regulatory organizer in AJs and related junctions in epithelial cells and cardiomyocytes, we hypothesize that the integration of Pkp2 into AJs of “soft tissue tumor” cells also can serve functions in the upregulation of proliferation, the promotion of malignant growth in general as well as the close‐packing of diverse kinds of cells and the metastatic behavior of such tumors. We propose to examine its presence in transformed mesenchymal cells and related tumors and to use it as an additional diagnostic criterion. © 2009 UICC
Cooperative interaction between protein inhibitor of activated signal transducer and activator of transcription‐3 with epidermal growth factor receptor blockade in lung cancer
Authors: Kluge Amy , Dabir Snehal , Kern Jeffrey , Nethery David , Halmos Balazs , Ma Patrick , Dowlati Afshin
Published: May 2009

Epidermal Growth Factor Receptor (EGFR) targeting in nonsmall cell lung cancer (NSCLC) is an established treatment modality; however, it only benefits a minority of patients. STAT3 (signal transducer and activator of transcription‐3) plays an important role in the oncogenic signal transduction pathway of NSCLC. Inhibition of STAT3 results in NSCLC growth inhibition and apoptosis. We have previously shown that combined inhibition of EGFR and STAT3 by small molecules resulted in improved therapeutic efficacy as compared with blocking EGFR alone. However, the STAT3 protein has a number of endogenous negative regulators including PIAS3 (Protein Inhibitor of Activated STAT3). In this study, we investigated for the first time the role of PIAS3 in modulating oncogenic EGFR‐STAT3 signaling pathway in lung cancer and the anti‐proliferative effect of using PIAS3 in conjunction with EGFR blockade in NSCLC. We demonstrate that PIAS3 is expressed in variable degrees in all NSCLC cells. EGF and IL‐6 stimulation resulted in the association of PIAS3 with STAT3. The PIAS3/STAT3 complex then bound the STAT3 DNA binding sequence resulting in STAT3 regulated gene expression. Over‐expression of PIAS3, using a PIAS3 expression construct, decreases STAT3 transcriptional activity. Furthermore, over‐expression of PIAS3 consistently decreased proliferation. EGFR blockade and PIAS3 over‐expression in combination had significantly greater anti‐proliferative effects as compared with either EGFR blockade or PIAS3 over‐expression alone. In conclusion, PIAS3 is expressed in NSCLC cell lines and its over‐expression decreased STAT3 transcriptional activity, decreased proliferation of NSCLC cells and when used in conjunction with EGFR inhibitors, increased the anti‐proliferative effects. © 2009 UICC
Dietary glucosinolate intake and risk of prostate cancer in the EPIC‐Heidelberg cohort study
Authors: Steinbrecher Astrid , Nimptsch Katharina , Hüsing Anika , Rohrmann Sabine , Linseisen Jakob
Published: May 2009

Glucosinolates (GLS) are secondary plant metabolites occurring in cruciferous vegetables. Their biologically active break‐down products show cancer preventive properties in animal and cell studies. So far, epidemiologic studies, using consumption of cruciferous vegetables as proxy for GLS intake, yielded inconsistent results. Here, we evaluated the association between dietary intake of GLS in comparison with consumption data of GLS‐containing foods and the risk of prostate cancer. The study population comprised 11,405 male participants of the prospective EPIC‐Heidelberg cohort study. During a mean follow‐up time of 9.4 years, 328 incident cases of prostate cancer occurred. At recruitment, habitual food consumption was assessed by a validated food frequency questionnaire, and intake of individual GLS was estimated by means of a newly compiled database on food content of GLS. Adjusted hazard ratios (HR) for prostate cancer were calculated using the Cox proportional hazard model. Median daily intake of total GLS was 7.9 mg/day (interquartile range 5.1–11.9 mg/day). The risk of prostate cancer decreased significantly over quartiles of total GLS intake (multivariate HR [4th vs. 1st quartile] 0.68, 95% CI 0.48–0.97, ptrend 0.03). Associations with GLS‐containing food intake were weaker. Among GLS subgroups, aliphatic GLS showed the strongest inverse association with cancer risk. Analyses stratified by tumor stage and grade gave hint to inverse associations for localized and low‐grade cancers. This study shows an inverse association between dietary intake of GLS and the risk of prostate cancer. Because this is the first prospective study using individual GLS intake data, confirmation in other studies is warranted. © 2009 UICC
Down‐regulation of HLA Class I and NKG2D ligands through a concerted action of MAPK and DNA methyltransferases in colorectal cancer cells
Authors: Sers Christine , Kuner Ruprecht , Falk Christine S. , Lund Per , Sueltmann Holger , Braun Monika , Buness Andreas , Ruschhaupt Markus , Conrad Janine , Mang‐Fatehi Shila , Stelniec Iwona , Krapfenbauer Ulf , Poustka Annemarie , Schäfer Reinhold
Published: May 2009

Most malignant features of cancer cells are triggered by activated oncogenes and the loss of tumor suppressors due to mutation or epigenetic inactivation. It is still unclear, to what extend the escape of emerging cancer cells from recognition and elimination by the immune system is determined by similar mechanisms. We compared the transcriptomes of HCT116 colorectal cancer cells deficient in DNA methyltransferases (DNMTs) and of cells, in which the RAS pathway as the major growth‐promoting signaling system is blocked by inhibition of MAPK. We identified the MHC Class I genes HLA‐A1/A2 and the ULBP2 gene encoding 1 of the 8 known ligands of the activating NK receptor NKG2D among a cluster of immune genes up‐regulated under the conditions of both DNMT‐deficiency and MEK‐inhibition. Bisulphite sequencing analyses of HCT116 with DNMT deficiency or after MEK‐inhibition showed that de‐methylation of the ULPB2 promoter correlated with its enhanced surface expression. The HLA‐A promoters were not methylated indicating that components of the HLA assembly machinery were also suppressed in DNMT‐deficient and MEK‐inhibited cells. Increased HLA‐A2 surface expression was correlated with enhanced recognition and lysis by A2‐specific CTL. On the contrary, elevated ULBP2 expression was not reflected by enhanced recognition and lysis by NK cells. Cosuppression of HLA Class I and NKG2D ligands and genes encoding peptide transporters or proteasomal genes mediates a strong functional link between RAS activation, DNMT activity and disruption of the antigen presenting system controlling immune recognition in colorectal cancer cells. © 2009 UICC
Mesenchymal stem cell modification of endothelial matrix regulates their vascular differentiation
Authors: Lozito Thomas P. , Taboas Juan M. , Kuo Catherine K. , Tuan Rocky S.
Published: May 2009

Mesenchymal stem cells (MSCs) respond to a variety of differentiation signal provided by their local environments. A large portion of these signals originate from the extracellular matrix (ECM). At the same time, MSCs secrete various matrix‐altering agents, including proteases, that alter ECM‐encoded differentiation signals. Here we investigated the interactions between MSC and ECM produced by endothelial cells (EC‐matrix), focusing not only on the differentiation signals provided by EC‐matrix, but also on MSC‐alteration of these signals and the resultant affects on MSC differentiation. MSCs were cultured on EC‐matrix modified in one of three distinct ways. First, MSCs cultured on native EC‐matrix underwent endothelial cell (EC) differentiation early during the culture period and smooth muscle cell (SMC) differentiation at later time points. Second, MSCs cultured on crosslinked EC‐matrix, which is resistant to MSC modification, differentiated towards an EC lineage only. Third, MSCs cultured on EC‐matrix pre‐modified by MSCs underwent SMC‐differentiation only. These MSC‐induced matrix alterations were found to deplete the factors responsible for EC‐differentiation, yet activate the SMC‐differentiation factors. In conclusion, our results demonstrate that the EC‐matrix contains factors that support MSC differentiation into both ECs and SMCs, and that these factors are modified by MSC‐secreted agents. By analyzing the framework by which EC‐matrix regulates differentiation in MSCs, we have uncovered evidence of a feedback system in which MSCs are able to alter the very matrix signals acting upon them. J. Cell. Biochem. 107: 706–713, 2009. Published 2009 Wiley‐Liss, Inc.
Simulated microgravity decreases DNA repair capacity and induces DNA damage in human lymphocytes
Authors: Kumari Ragini , Singh Kamaleshwar P. , DuMond James W.
Published: May 2009

The effect of simulated microgravity on DNA damage and apoptosis is still controversial. The objective of this study was to test whether simulated microgravity conditions affect the expression of genes for DNA repair and apoptosis. To achieve this objective, human lymphocyte cells were grown in a NASA‐developed rotating wall vessel (RWV) bioreactor that simulates microgravity. The same cell line was grown in parallel under normal gravitational conditions in culture flasks. The effect of microgravity on the expression of genes was measured by quantitative real‐time PCR while DNA damage was examined by comet assay. The result of this study revealed that exposure to simulated microgravity condition decreases the expression of DNA repair genes. Mismatch repair (MMR) class of DNA repair pathway were more susceptible to microgravity condition‐induced gene expression changes than base excision repair (BER) and nucleotide excision repair (NER) class of DNA repair genes. Downregulation of genes involved in cell proliferation (CyclinD1 and PCNA) and apoptosis (Bax) was also observed. Microgravity‐induced changes in the expression of some of these genes were further verified at the protein level by Western blot analysis. The findings of this study suggest that microgravity may induce alterations in the expression of these DNA repair genes resulting in accumulation of DNA damage. Reduced expression of cell‐cycle genes suggests that microgravity may cause a reduction in cell growth. Downregulation of pro‐apoptotic genes further suggests that extended exposure to microgravity may result in a reduction in the cells' ability to undergo apoptosis. Any resistance to apoptosis seen in cells with damaged DNA may eventually lead to malignant transformation of those cells. J. Cell. Biochem. 107: 723–731, 2009. © 2009 Wiley‐Liss, Inc.
Caspases and p53 modulate FOXO3A/Id1 signaling during mouse neural stem cell differentiation
Authors: Aranha Márcia M. , Solá Susana , Low Walter C. , Steer Clifford J. , Rodrigues Cecília M.P.
Published: May 2009

Neural stem cells (NSCs) differentiate into neurons and glia, and a large percentage undergoes apoptosis. The engagement and activity of apoptotic pathways may favor either cell death or differentiation. In addition, Akt represses differentiation by up‐regulating the inhibitor of differentiation 1 (Id1), through phosphorylation of its repressor FOXO3A. The aim of this study was to investigate the potential cross‐talk between apoptosis and proliferation during mouse NSC differentiation. We determined the time of neurogenesis and gliogenesis using neuronal β‐III tubulin and astroglial GFAP to confirm that both processes occurred at ∼3 and 8 days, respectively. p‐Akt, p‐FOXO3A, and Id1 were significantly reduced throughout differentiation. Caspase‐3 processing, p53 phosphorylation, and p53 transcriptional activation increased at 3 days of differentiation, with no evidence of apoptosis. Importantly, in cells exposed to the pancaspase inhibitor z‐VAD.fmk, p‐FOXO3A and Id1 were no longer down‐regulated, p53 phosphorylation and transcriptional activation were reduced, while neurogenesis and gliogenesis were significantly delayed. The effect of siRNA‐mediated silencing of p53 on FOXO3A/Id1 was similar to that of z‐VAD.fmk only at 3 days of differentiation. Interestingly, caspase inhibition further increased the effect of p53 knockdown during neurogenesis. In conclusion, apoptosis‐associated factors such as caspases and p53 temporally modulate FOXO3A/Id1 signaling and differentiation of mouse NSCs. J. Cell. Biochem. 107: 748–758, 2009. © 2009 Wiley‐Liss, Inc.
Regulation and function of proline oxidase under nutrient stress
Authors: Pandhare Jui , Donald Steven P. , Cooper Sandra K. , Phang James M.
Published: May 2009

Under conditions of nutrient stress, cells switch to a survival mode catabolizing cellular and tissue constituents for energy. Proline metabolism is especially important in nutrient stress because proline is readily available from the breakdown of extracellular matrix (ECM), and the degradation of proline through the proline cycle initiated by proline oxidase (POX), a mitochondrial inner membrane enzyme, can generate ATP. This degradative pathway generates glutamate and α‐ketoglutarate, products that can play an anaplerotic role for the TCA cycle. In addition the proline cycle is in a metabolic interlock with the pentose phosphate pathway providing another bioenergetic mechanism. Herein we have investigated the role of proline metabolism in conditions of nutrient stress in the RKO colorectal cancer cell line. The induction of stress either by glucose withdrawal or by treatment with rapamycin, stimulated degradation of proline and increased POX catalytic activity. Under these conditions POX was responsible, at least in part, for maintenance of ATP levels. Activation of AMP‐activated protein kinase (AMPK), the cellular energy sensor, by 5‐aminoimidazole‐4‐carboxamide ribonucleoside (AICAR), also markedly upregulated POX and increased POX‐dependent ATP levels, further supporting its role during stress. Glucose deprivation increased intracellular proline levels, and expression of POX activated the pentose phosphate pathway. Together, these results suggest that the induction of proline cycle under conditions of nutrient stress may be a mechanism by which cells switch to a catabolic mode for maintaining cellular energy levels. J. Cell. Biochem. 107: 759–768, 2009. © 2009 Wiley‐Liss, Inc.
FGF‐8b induces growth and rich vascularization in an orthotopic PC‐3 model of prostate cancer
Authors: Valta Maija P. , Tuomela Johanna , Vuorikoski Heikki , Loponen Niina , Väänänen Riina‐Minna , Pettersson Kim , Väänänen H. Kalervo , Härkönen Pirkko L.
Published: May 2009

Fibroblast growth factor 8 (FGF‐8) is expressed at an increased level in a high proportion of prostate cancers and it is associated with a poor prognosis of the disease. Our aim was to study the effects of FGF‐8b on proliferation of PC‐3 prostate cancer cells and growth of PC‐3 tumors, and to identify FGF‐8b‐associated molecular targets. Expression of ectopic FGF‐8b in PC‐3 cells caused a 1.5‐fold increase in cell proliferation in vitro and a four‐ to fivefold increase in the size of subcutaneous and orthotopic prostate tumors in nude mice. Tumors expressing FGF‐8b showed a characteristic morphology with a very rich network of capillaries. This was associated with increased spread of the cancer cells to the lungs as measured by RT‐qPCR of FGF‐8b mRNA. Microarray analyses revealed significantly altered, up‐ and downregulated, genes in PC‐3 cell cultures (169 genes) and in orthotopic PC‐3 tumors (61 genes). IPA network analysis of the upregulated genes showed the strongest association with development, cell proliferation (CRIP1, SHC1), angiogenesis (CCL2, DDAH2), bone metastasis (SPP1), cell‐to‐cell signaling and energy production, and the downregulated genes associated with differentiation (DKK‐1, VDR) and cell death (CYCS). The changes in gene expression were confirmed by RT‐qPCR. In conclusion, our results demonstrate that FGF‐8b increases the growth and angiogenesis of orthotopic prostate tumors. The associated gene expression signature suggests potential mediators for FGF‐8b actions on prostate cancer progression and metastasis. J. Cell. Biochem. 107: 769–784, 2009. © 2009 Wiley‐Liss, Inc.
A proteomic approach to the identification of molecular targets in subsequent apoptosis of HEL cells after diosgenin‐induced megakaryocytic differentiation
Authors: Cailleteau Clementine , Liagre Bertrand , Beneytout Jean‐L.
Published: May 2009

Diosgenin is a plant steroid which is able to induce megakaryocytic differentiation of human erythroleukemia (HEL) cells followed by apoptosis at a later stage. Apoptosis markers and phospho‐kinases involved during the subsequent apoptosis of megakaryocytes after diosgenin‐induced differentiation in these cells were detected using a proteomic approach. In mature megakaryocytes undergoing apoptosis, we observed increased expression of intrinsic apoptosis markers such as Bax/Bcl‐2 ratio and cleaved caspase‐9 as well as extrinsic apoptosis markers including cell death receptors and cleaved caspase‐8. Furthermore, we demonstrated the link between both apoptotic pathways by Bid cleavage and confirmed the executive phase of apoptosis by caspase‐3 cleavage. For the first time, we examined kinase activation and showed that kinases including Src, Tor, Akt, CREB, RSK and Chk2 may be implicated in signalling of subsequent apoptosis of mature megakaryocytes after diosgenin‐induced differentiation of HEL cells. J. Cell. Biochem. 107: 785–796, 2009. © 2009 Wiley‐Liss, Inc.
Caspase‐3‐mediated cyclic stretch‐induced myoblast apoptosis via a Fas/FasL‐independent signaling pathway during myogenesis
Authors: Liu Jiaqiang , Liu Jing , Mao Jing , Yuan Xiao , Lin Zhu , Li Yongming
Published: May 2009

Skeletal muscle cells are exposed to mechanical stretch during embryogenesis. Increased stretch may contribute to cell death, and the molecular regulation by stretch remains incompletely understood. The aim of this study was to investigate the effects of cyclic stretch on cell death and apoptosis in myoblast using a Flexercell Strain Unit. Apoptosis was studied by annexin V binding and PI staining, DNA size analysis, electron microphotograph, and caspase assays. Fas/FasL expression was determined by Western blot. When myoblasts were cultured on a flexible membrane and subjected to cyclic strain stress, apoptosis was observed in a time‐dependent manner. We also determined that stretch induced cleavage of caspase‐3 and increased caspase‐3 activity. Caspase‐3 inhibition reduced stretch‐induced apoptosis. Protein levels of Fas and FasL remained unchanged. Our findings implicated that stretch‐induced cell death is an apoptotic event, and that the activation of caspase cascades is required in stretch‐induced cell apoptosis. Furthermore, we had provided evidence that caspase‐3 mediated cyclic stretch‐induced myoblast apoptosis. Mechanical forces induced activation of caspase‐3 via signaling pathways independent of Fas/FasL system. J. Cell. Biochem. 107: 834–844, 2009. © 2009 Wiley‐Liss, Inc.
Increased bone resorption and osteopenia in Dlx5 heterozygous mice
Authors: Samee Nadeem , Geoffroy Valérie , Marty Caroline , Schiltz Corinne , Vieux‐Rochas Maxence , Clément‐Lacroix Philippe , Belleville Cécile , Levi Giovanni , de Vernejoul Marie‐Christine
Published: May 2009

Distal‐less (Dlx) homeobox transcription factors play a central role in the control of osteogenesis. In particular, Dlx5 regulates osteoblasts/osteoclasts coupling during perinatal bone formation. We analyze here the effect of Dlx5 allelic reduction in the control of bone remodeling. We first show that Dlx5 expression persists during postnatal bone development. We then compare the skeletal phenotype of 10‐ and 20‐week‐old Dlx5+/− mice to that of wild‐type (WT) littermates. Dlx5+/− male mice exhibit lower bone mineral density (BMD) at both ages while only 20‐week‐old females are affected. µCT analyses reveal a reduction in cortical thickness of femoral midshafts in Dlx5+/− mice. Histomorphometry on distal femora shows no changes in trabecular structure and confirms a reduction in Dlx5+/− cortical thickness. The cortical decrease of 10‐week‐old mice does not derive from a reduction in periosteal bone apposition, but results from increased bone resorption with a significantly higher number of endosteal osteoclasts per bone surface and a larger marrow diameter. Urinary level of deoxypyridinoline is also higher in heterozygous mice confirming an increase in bone resorption activity. Our findings might be relevant for understanding complex, multifactorial diseases such as osteoporosis in which quantitative deregulation of gene expression leads to disruption of bone homeostasis. J. Cell. Biochem. 107: 865–872, 2009. © 2009 Wiley‐Liss, Inc.
Thyroid state and tolerance of mammalian myocardium to hypoxia
Authors: Brooks Wesley W. , Cicogna Antonio C. , Conrad Chester H. , Robinson Kathleen G. , Sen Subha , Bing Oscar H.L.
Published: May 2009

Thyroid hormone is known to affect myocardial glycogen stores and thereby possibly limit anaerobic performance of mammalian cardiac muscle. Thyroid hormone administration (3,5,3′‐triiodo‐L‐thyroxine, 300 µg/kg/day, sc) for 10 days decreased left ventricle (LV) glycogen concentration relative to euthyroid animals (2.78±0.46 vs. 4.28±0.29 mg/g of LV (mean±SEM)) while increasing the percent of V1 myosin isozyme, contractile activity and cardiac mass. In contrast, thyroidectomy increased myocardial glycogen stores (8.50±0.56 mg/g of LV) and shifted the myosin isozyme toward V3, prolonged contractile activity and decreased LV mass. Thyroxine administration for 3, 7 and 10 days to thyroidectomized animals progressively decreased contractile duration and increased LV mass. Thyroxine administration for 3 or 7 days to thyroidectomized rats did not reduce glycogen stores (7.75±1.02 and 9.62±1.16 mg/g of LV, respectively), whereas myocardial glycogen declined to 3.30±0.58 mg/g of LV after 10 days of treatment. During hypoxia, cardiac muscle from thyroidectomized rats maintained greater active force and developed less contracture relative to euthyroid and, to a greater extent, than hyperthyroid rats. Removal of glucose from the bath decreased anaerobic performance and impaired recovery; however, myocardium from thyroidectomized rats remained more tolerant to hypoxia than the euthyroid group. Overall, the intrinsic LV glycogen content was positively correlated to anaerobic performance. These data demonstrate that the thyroid state profoundly affects myocardial growth, contractility and anaerobic performance of rat myocardium. Although energy demand may affect function during hypoxia, anaerobic substrate reserve (cardiac glycogen concentration) appears to be the primary factor determining tolerance to hypoxic stress. J. Exp. Zool. 311A:399–407, 2009. © 2009 Wiley‐Liss, Inc.
Retention time of attenuated response to diacetyl after pre‐exposure to diacetyl in Caenorhabditis elegans
Authors: Matsuura Tetsuya , Suzuki Seiko , Musashino Ayaka , Kanno Ryo , Ichinose Mitsuyuki
Published: May 2009

The retention time of attenuated chemotactic response to continuous presentation of odorant diacetyl was investigated in the nematode Caenorhabditis elegans. The level of chemotactic response of nematodes pre‐exposed to diacetyl for 90 min was significantly smaller than that of nonexposed control nematodes. In this study, wild‐type (N2) nematodes were maintained at 15, 20 and 25°C after pre‐exposure to diacetyl. At 20°C, there was a decrease in response to diacetyl continuing for up to 6 hr after pre‐exposure to the chemical, but not up to 12 hr. Interestingly, the decrease in response to diacetyl did not continue up to 2 hr in nematodes bred at 15°C, although it continued beyond 12 hr in nematodes bred at 25°C. These results indicate that the retention time of attenuated chemotactic response to diacetyl is dependent on the environmental breeding temperature of nematodes. The breeding temperature correlated with aging speed of nematodes, suggesting that a short life span (higher aging speed) prolongs the retention time of attenuated chemotactic response to diacetyl after pre‐exposure to diacetyl. In the long‐lived daf‐2, age‐1, clk‐1 and isp‐1 mutants, the effect of diacetyl did not continue up to 2 hr. The short‐lived daf‐16, daf‐18, mev‐1 and gas‐1 mutants showed a longer duration of decrease in response to diacetyl, that is, the retention time of attenuated chemotactic response to diacetyl continued beyond 12 hr. There is a possibility that the duration of decrease in response to diacetyl after pre‐exposure to diacetyl was inversely related to the length of nematodes' life span. J. Exp. Zool. 311A:483–495, 2009. © 2009 Wiley‐Liss, Inc.
Evolutionary conservation of mammalian HTRA3 and its developmental regulation in the rat ovary
Authors: Bowden Marissa , Drummond Ann E. , Salamonsen Lois A. , Findlay Jock K. , Nie Guiying
Published: May 2009

The high‐temperature requirement factor A (HtrA) family of serine proteases is evolutionarily conserved from bacteria to mammals. We have previously identified Htra3 in the mouse and human (HTRA3) and reported its expression in the ovary. In this study, we analyzed the rat Htra3 gene and determined its developmental regulation in the rat ovary. We localized the rat Htra3 gene on chromosome 14q21 and identified two alternatively spliced mRNA variants. The two protein sequences deduced from these mRNAs enabled the prediction of the domain organization of the two protein isoforms. Our comparative analysis has established that the key gene features of Htra3 including its genomic structure, intron–exon junction and alternative splicing are well conserved among the mouse, rat and human. The similarities are even higher at the levels of primary protein sequence and protein domain architecture, suggesting that the functions of Htra3 are highly conserved during evolution from rodents to primates. We demonstrate that Htra3 expression in the rat ovary is developmentally regulated; expression was initiated on day 12 after birth and up‐regulated during ovarian maturation with the highest levels found in the mature cycling ovary. In the mature ovary, Htra3 was expressed in granulosa cells, in a follicle‐stage specific manner, with the level of expression being dependent on the positioning of the granulosa cells relative to the oocyte in late stage follicles. The luteinizing granulosa cells of the corpus luteum expressed the highest levels of Htra3. Collectively, these results suggest an important role for Htra3 in ovarian development, granulosa cell differentiation and luteinization. J. Exp. Zool. (Mol. Dev. Evol.) 312B:701–713, 2009. © 2009 Wiley‐Liss, Inc.
Innovative e‐commerce model for food tourism products
Authors: Huang Ting‐Chung , Lee Timothy Jeonglyeol , Lee Kuan‐Huei
Published: May 2009

The applications and opportunities for e‐commerce are increasing. The unique features of the Internet have changed the styles and competition of enterprises. The key factor for the survival of enterprises in this competitive environment is whether they know how to make use of these features to maximise advantages and to make profits. Different enterprises' e‐commerce business models were investigated in the food souvenir industry in Hualien, Taiwan. This study combines the characteristics of network marketing and develops a business model for e‐commerce. This innovative business model in e‐commerce suggests a new paradigm for traditional industries. Copyright © 2009 John Wiley & Sons, Ltd.
Laser cooling of solids [Laser Photon. Rev. 3, No. 1–2, 67–84 (2009)]
Authors: Sheik‐Bahae M. , Epstein R.I.
Published: May 2009

Fig. 7b and Figs. 14a and b in the paper published in Laser Photon. Rev. 3, 67–84 have not been referenced completely. Please find the correct figure captions here.
Near‐wall hydrodynamic effects related to flow‐induced localized corrosion
Authors: Yabuki A.
Published: May 2009

The relationship between near‐wall hydrodynamic conditions and flow‐induced localized corrosion of copper alloys was investigated. Flow‐induced localized corrosion tests for copper alloys were conducted in corrosive solutions using a jet‐in‐slit testing apparatus, in which various hydrodynamic conditions were reproduced. To evaluate local damage, the profiles of the specimens were measured using a surface roughness meter. In addition, the near‐wall hydrodynamic conditions on the material surface in the apparatus were measured by pressure gauges to determine the distribution of near‐wall velocities and velocity fluctuations. In the equation used to predict corrosion damage, three types of hydrodynamic conditions were applied as parameters related to the mass transfer coefficient in the film of corrosion products. The damage profiles calculated from the equation could be fitted to that obtained from the corrosion test.
Effect of the long‐term service of the gas pipeline on the properties of the ferrite–pearlite steel
Authors: Nykyforchyn H. , Lunarska E. , Tsyrulnyk O. , Nikiforov K. , Gabetta G.
Published: May 2009

The thorough mechanical, corrosion‐mechanical, hydrogen permeation studies of X52 steel in as‐received condition and after 30 years of service in gas pipeline have shown the degradation of the bulk metal properties due to the exploitation. The structure degradation of exploited steels decreased the resistance to crack propagation, to stress corrosion cracking (SCC), HE and HIBC. The exploited steel exhibited specific anomalies of mechanical behaviour: (1) decrease in resistance to brittle fracture with simultaneous decrease in hardness; and (2) the opposite change of the plasticity parameters: decrease in the RA accompanied by the increase in elongation. Deformation ageing and formation of micro defects, assisted by entering and accumulated hydrogen evolved in corrosion processes which takes place in brine deposited inside the pipes, have been proposed to be responsible for the metal degradation and specific modification of the properties during the long‐term service of pipes. The extent of the steel degradation not being able to be detected by the standardized mechanical properties and routine microstructure observation can be efficiently determined by the specially modified methods and conditions. The information may be used in assessment of the conditions and of the life‐time of operated and newly constructed gas pipelines.
Corrosion characteristics of Al‐Si‐Mg/SiCp composites with varying Si/Mg molar ratio in neutral chloride solutions
Authors: Escalera‐Lozano R. , Pech‐Canul M. A. , Pech‐Canul M. I. , Quintana P.
Published: May 2009

The corrosion resistance of Al‐Mg‐Si/SiCp composites produced by the pressureless infiltration method [using SiCp preforms with 50% porosity containing rice hull ash (RHA) and four custom‐made alloys with varying Si/Mg molar ratio] was evaluated in neutral 0.1 M NaCl solutions. The deleterious phase Al4C3 was successfully suppressed in composites with Si/Mg molar ratios of 0.89 and 1.05, but not in those with lower Si/Mg molar ratios (0.12 and 0.49). Results of cyclic polarizations in deareated 0.1 M NaCl solutions showed that with increasing Si/Mg molar ratio, passive current density increased but pitting susceptibility decreased both for reinforced and unreinforced alloys. Immersion tests in aerated 0.1 M NaCl showed that for composites with Si/Mg molar ratios of 0.12 and 0.49 chemical degradation by hydrolysis of Al4C3 was followed by intense anodic dissolution at the matrix–reinforcement interface, while composites corresponding to Si/Mg molar ratios of 0.89 and 1.05 did not exhibit intense localized attack. Possible reasons for the improvement in resistance to localized corrosion are discussed.
The cyclic oxidation behavior of the single crystal TMS‐82+ superalloy in humidified air
Authors: Wu Y. , Narita T.
Published: May 2009

The cyclic oxidation behavior of a single crystal Ni‐based superalloy TMS‐82+ was studied at 800 and 900 °C for 200 h in water vapor (air plus 15% H2O). Regardless of the exposure temperature, time‐dependence of the growth rate of the scale for the superalloy was fitted by a subparabolic relationship. The oxidation rate was enhanced with increase in exposure temperature, which was evidenced by a higher mass gain and thicker scale. The oxides on the specimen at 800 °C consisted of (Ni,Co)O, CrTaO4, AlTaO4, Cr2O3, and θ‐Al2O3, whereas for the specimen exposed at 900 °C, spinels of NiCr2O4 and (Ni,Co)Al2O4 as well as α‐Al2O3 were observed. An innermost dense α‐Al2O3 layer was responsible for a stable growth rate of the scale after the initial rapid oxidation.
Rainbow fringes around crevice corrosion formed on stainless steel AISI 316 after ennoblement in seawater
Authors: Wang W. , Zhang X. , Wang J.
Published: May 2009

The crevice corrosion occurrence probability of stainless steel (SS) AISI 316 was increased under ennoblement condition due to chemically added H2O2 into seawater. The H2O2 was used to simulate the important factor causing ennoblement in natural marine biofilm. Morphology of the crevice corrosion was observed using an incident‐light source microscopy. Some interesting “rainbow” fringes were observed around micro‐crevices. The mechanism was discussed from the ions diffusion and potential distribution during the crevice formation. This result shows that under ennoblement condition the colored fringe is a distinct characteristic of the morphology of localized corrosion for stainless steel.
Regulation of peroxisome proliferator‐activated receptor‐β/δ by the APC/β‐CATENIN pathway and nonsteroidal antiinflammatory drugs
Authors: Foreman Jennifer E. , Sorg Joseph M. , McGinnis Kathleen S. , Rigas Basil , Williams Jennie L. , Clapper Margie L. , Gonzalez Frank J. , Peters Jeffrey M.
Published: May 2009

Studies indicate that peroxisome proliferator‐activated receptor‐β/δ (PPARβ/δ) can either attenuate or potentiate colon cancer. One hypothesis suggests that PPARβ/δ is upregulated by the adenomatous polyposis coli (APC)/β‐CATENIN pathway and a related hypothesis suggests that PPARβ/δ is downregulated by nonsteroidal antiinflammatory drugs (NSAIDs). The present study examined these possibilities using in vivo and in vitro models. While APC/β‐CATENIN‐dependent expression of CYCLIN D1 was observed in vivo and in vitro, expression of PPARβ/δ was not different in colon or intestinal polyps from wild‐type or Apcmin heterozygous mice or in human colon cancer cell lines with mutations in APC and/or β‐CATENIN. No difference in the level of PPARβ/δ was found in colon from wild‐type or Apcmin heterozygous mice following treatment with NO‐donating aspirin (NO‐ASA). NSAIDs inhibited cell growth in RKO (wild‐type APC) and DLD1 (mutant APC) human colon cancer cell lines but expression of PPARβ/δ was not downregulated in these cell lines in response to a broad concentration range of celecoxib, indomethacin, NS‐398, or nimesulide. However, indomethacin caused an increase in PPARβ/δ mRNA and protein that was accompanied with increased expression of a known PPARβ/δ target gene. Interestingly, expression of PPARα was also increased in the human colon cancer cell lines by several NSAIDs at the highest concentration examined. Results from these studies provide additional evidence indicating that PPARβ/δ is not upregulated by the APC/β‐CATENIN pathway. Further, these studies suggest that increased PPARβ/δ and/or PPARα by NSAIDs in human colon cancer cell lines could contribute to the mechanisms underlying the chemopreventive effects of NSAIDs. Mol. Carcinog. © 2009 Wiley‐Liss, Inc.