bluuebunny/crossref_metadata_2025 huggingface dataset:
Strength Enhancement of Nanostructured Organogels through Inclusion of Phthalocyanine‐Containing Complementary Organogelator Structures and In Situ Cross‐Linking by Click Chemistry
Authors: Díaz David Díaz , Cid Juan José , Vázquez Purificación , Torres Tomás
Published: August 2008

Stable photoactive organogels were successfully prepared by a two‐step sequence involving: 1) formation of thermoreversible organogels by use of a combination of low‐molecular‐weight organogelators (LMOGs) and ZnII–phthalocyanine (ZnII–Pc) moieties containing complementary organogelator structures, and 2) strength enhancement of the gels by in situ cross‐linking with the aid of CuI‐catalysed azide–alkyne [3+2] cycloadditions (CuAACs). The optimum click reaction was carried out between a flexible C6 aliphatic diazide and a suitable dialkyne (molar ratio 1:1) added in a low proportion relative to the organogelator system [LMOG+ZnIIPc]. The dialkyne unit was incorporated into a molecule resembling the LMOGs structure in such a way that it could also participate in the self‐assembly of [LMOG+ZnIIPc]. The significant compatibility of the multicomponent photoactive organogels towards this strengthening through CuAACs allowed their sol‐to‐gel transition temperatures (Tgel) to be enhanced by up to 15 °C. The Tgel values estimated by the “inverse flow method” were in good agreement with the values obtained by differential scanning calorimetry (DSC). Rheological measurements confirmed the viscoelastic, rigid, and brittle natures of all Pc‐containing gels. Transmission and scanning electron microscopy (TEM, SEM) and atomic force microscopy (AFM) revealed the fibrilar nature of the gels and the morphological changes upon cross‐linking by CuAAC. Emission of a red luminescence from the dry nanoscale fibrous structure—due to the self‐assembly of the Pc‐containing compounds in the organogel fibres—was directly observed by confocal laser scanning microscopy (CLSM). The optical properties were studied by UV/Vis and fluorescence spectroscopy. Fluorescence, Fourier‐transform infrared (FTIR) and circular dichroism (CD) measurements were also carried out to complete the physicochemical characterization of selected gels. As a proof of concept, two different organogelators (cholesterol‐ and diamide‐based LMOGs) were successfully used to validate the general strategy.
Heterogeneous Gold Catalysts for Efficient Access to Functionalized Lactones
Authors: Neaţu Florentina , Li Zhi , Richards Ryan , Toullec Patrick Y. , Genêt Jean‐Pierre , Dumbuya Karifala , Gottfried J. Michael , Steinrück Hans‐Peter , Pârvulescu Vasile I. , Michelet Véronique
Published: August 2008

A novel class of heterogeneous gold catalysts supported on zeolite beta‐NH4+ was prepared by the deposition–precipitation method. This new class of catalyst showed interesting catalytic activities for the intramolecular cycloisomerization of γ‐acetylenic carboxylic acids leading to functionalized γ‐alkylidene γ‐butyrolactones. Analysis of the supported gold species with in situ X‐ray photoelectron spectroscopy (in situ XPS) suggests that cationic Au (possibly AuIII) can play an important role in such reactions. The high discrepancy in catalyst stability in favor of the Au supported on the zeolite system over bulk Au2O3 is explained by 1) the size of the particles and 2) the reversibility of the redox deactivating process (AuIII→AuI) in the presence of oxygen for the supported system. The efficiency of this system allowed reaction under mild heterogeneous conditions. The potential for catalyst recycling was also highlighted.
Analyse qualitative des facteurs d'influence sur l'adhésion des employés à l'implantation d'un système d'information dans le secteur public : vers un modèle conceptuel
Authors: Ouadahi Jamal
Published: August 2008

This study examines the factors that lead employees to endorse or resist the introduction of a new information system (IS). Findings suggest that attitudes toward adopting IS are related to psychological characteristics of the potential adopters, including, open‐mindedness, self‐efficacy, interest in the information and communication technology, and time remaining before retirement. Also figuring prominently in influencing attitudes are the end‐users' perceptions and expectations with respect to project management, IS quality, IS usefulness, and its effects on organizational positions, work organization, performance, skills, jobs, and worker health. Finally, user attitudes also relate to features of change management practices, including leadership, training, support, recognition, communication, and participation. An integrative conceptual model of IS user adoption is proposed and suggestions for future research are offered. Copyright © 2008 ASAC. Published by John Wiley & Sons, Ltd.
Developmental and spatial expression pattern of α‐Taxilin in the rat central nervous system
Authors: Sakakibara Shin‐ichi , Nakadate Kazuhiko , Tanaka‐Nakadate Sawako , Yoshida Kenji , Nogami Satoru , Shirataki Hiromichi , Ueda Shuichi
Published: August 2008

α‐Taxilin has been identified as a binding partner of syntaxin family members and thus has been proposed to function in syntaxin‐mediated intracellular vesicle trafficking. However, the lack of detailed information concerning the cellular and subcellular localization of α‐taxilin impedes an understanding of the role of this protein. In the present study, we characterized α‐taxilin‐expressing cells in the rat CNS with a specific antibody. During embryonic development, α‐taxilin was prominently expressed in nestin‐positive neural stem cells in vivo and in vitro. As CNS development proceeded, the α‐taxilin expression level was rapidly down‐regulated. In the postnatal CNS, α‐taxilin expression was almost confined to the neuronal lineage, with the highest levels of expression in motor neurons within the brainstem nuclei and spinal cord and in primary sensory neurons in mesencephalic trigeminal nucleus. At the cellular level, α‐taxilin was preferentially located in Nissl substance‐like structures with a tigroid or globular morphology within the soma and proximal to dendrites, but it was excluded from terminals. Combined staining with propidium iodide demonstrated that α‐taxilin distribution overlapped with the cytoplasmic compartment enriched in RNA species, suggesting a close association of α‐taxilin with actively translating ribosomes or polysomes in neurons. In agreement with this, a recent study indicated the preferential binding of α‐taxilin to the nascent polypeptide‐associated complex (αNAC), a dynamic component of the ribosomal exit tunnel in eukaryotic cells. Taken together, these findings suggest that α‐taxilin plays multiple roles in the generation and maintenance of neurons through modulation of the NAC‐mediated translational machinary and/or the syntaxin‐mediated vesicle traffic in the soma. J. Comp. Neurol. 511:65–80, 2008. © 2008 Wiley‐Liss, Inc.
Neuroanatomy of the complex tibial organ ofStenopelmatus(Orthoptera: Ensifera: Stenopelmatidae)
Authors: Strauß Johannes , Lakes‐Harlan Reinhard
Published: August 2008

Stenopelmatidae (or “Jerusalem crickets”) belong to the atympanate Ensifera, lacking hearing organs in the foreleg tibiae. Their phylogenetic position is controversial, either as a taxon in Tettigonioidea or within the clade of Gryllacridoidea. Similarly, the origin of tibial auditory systems in Ensifera is controversial. Therefore, we investigated the neuronal structures of the proximal tibiae ofStenopelmatus spec. with the hypothesis that internal sensory structures are similar to those in tympanate Ensifera. InStenopelmatusthe complex tibial organ consists of three neuronal parts: the subgenual organ, the intermediate organ, and a third part with linearly arranged neurons. This tripartite organization is also found in tympanate Ensifera, verifying our hypothesis. The third part of the sense organ found inStenopelmatuscan be regarded by the criterion of position as homologous to auditory receptors of hearing Tettigonioidea. This crista acustica homolog is found serially in all thoracic leg pairs and contains 20 ± 2 chordotonal neurons in the foreleg. The tibial organ was shown to be responsive to vibration, with a broad threshold of about 0.06 ms−2in a frequency range from 100–600 Hz. The central projection of tibial sensory neurons terminates into two equally sized lobes in the primary sensory neuropil, the medial ventral association center. The data are discussed comparatively to those of other Ensifera and mapped phylogenetically onto recently proposed phylogenies for Ensifera. The crista acustica homolog could represent a neuronal rudiment of a secondarily reduced ear, but neuronal features are also consistent with an evolutionary preadaptation. J. Comp. Neurol. 511:81–91, 2008. © 2008 Wiley‐Liss, Inc.
Envelope tracking power amplifier with static predistortion linearization
Authors: Rautio Timo , Harju Henri , Hietakangas Simo , Rahkonen Timo
Published: August 2008

This paper presents the design method, properties and driving techniques of a linear 0.5 W 1 GHz LDMOS power amplifier used in a supply modulated envelope tracking transmitter with real‐time predistortion. Causes of nonlinearities are identified, and various supply voltage drives are experimented. Measured results show that the power efficiency can be improved while maintaining high linearity. Copyright © 2008 John Wiley & Sons, Ltd.
Bone marrow or foetal liver cells fail to induce islet regeneration in diabetic Akita mice
Authors: Akashi Tomoyuki , Shigematsu Hirokazu , Hamamoto Yoshiyuki , Iwasaki Hiromi , Yatoh Shigeru , Bonner‐Weir Susan , Akashi Koichi , Weir Gordon C.
Published: August 2008

Background

In this study, we carried out bone marrow and foetal liver cell transplantation to determine if these cells could differentiate into pancreatic β‐cells or promote regeneration.

Methods

To exclude an artificial or immunological influence for induction of diabetes to recipients, Akita mice, which develop diabetes spontaneously,were used. In addition, we used mice harbouring the transgenic green fluorescent protein (GFP) reporter for insulin 1 gene as donors to mark donor‐derived β‐cells.

Results

All transplanted Akita mice after intravenous injection showed full donor chimerism in peripheral blood analysis. Their diabetic state represented by blood glucose levels did not change after transplantation. In spite of examination of more than 200 islets in each group, we could not find GFP‐positive cells in any of the recipients.

Conclusions

Bone marrow cells or foetal liver cells do not differentiate to new pancreatic β‐cells or promote regeneration in Akita mice, a non‐chemical or non‐immune model of diabetes. Copyright © 2008 John Wiley & Sons, Ltd.
Mild Oxidative Addition of C–H Bonds to a Hydrido‐Bridged Dinuclear Complex of Iridium(II) Induced by the Coordination of Heteroatomic Ligands
Authors: Takahashi Yoshinori , Fujita Ken‐ichi , Yamaguchi Ryohei
Published: August 2008

The oxidative addition of C–H bonds to a dinuclear complex of divalent iridium, [Cp*Ir(μ‐H)]2 (1), has been investigated. Reactions of 1 with phosphorus compounds containing a phenyl ring (PR1R2Ph) at ambient temperature gave novel five‐membered diiridacyclic [(Cp*IrH)2(μ‐H)(μ‐R1R2PC6H4)] [R1 = R2 = Me (2a); R1 = Me, R2 = Ph (2b); R1 = R2 = Ph (2c); R1 = R2 = OEt (2d); and R1 = OEt, R2 = Ph (2e)] complexes through ortho‐C–H activation of the phenyl ring bound to the phosphorus atom. The reaction of 1 with tripropylphosphane gave a new four‐membered diiridacyclic [(Cp*IrH)2(μ‐H)(μ‐Pr2PCHCH2CH3)] (3) complex in a similar manner. On the other hand, the reaction of 1 with triethyl phosphite gave a Cp*‐metalated product, [Ir(H)(P(OEt)3)(μ,η5,η1‐C5Me4CH2)(μ‐H)Ir(H)(Cp*)] (4), through C–H activation of a methyl group on one of the Cp* ligands. Furthermore, similar mild C–H activation reactions of 1 with sulfoxides have also been revealed. Thus, reactions of 1 with dimethyl sulfoxide and a couple of sulfoxides containing phenyl groups brought about the activation of the C–H bonds of a methyl group and a phenyl group to give [(Cp*IrH)2(μ‐H)(μ‐MeS(=O)CH2)] (5) and [(Cp*IrH)2(μ‐H)(μ‐RS(=O)C6H4)] [R = Me (6a) and R = Ph (6b)], respectively. The structures of 2a, 4, 5, and 6a have been confirmed by X‐ray analysis. A plausible reaction pathway for these C–H activation reactions has been proposed. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
The Added Value of Solid‐State Pb NMR Spectroscopy to Understand the 3D Structures of Pb Amino Acid Complexes
Authors: Gasque Laura , Verhoeven Michiel A. , Bernès Sylvain , Barrios Fabiola , Haasnoot Jaap G. , Reedijk Jan
Published: August 2008

Single‐crystal X‐ray diffraction and solid‐state 207Pb NMR spectroscopic experiments have been conducted on four lead amino acid complexes with nitrato or perchlorato counterions, namely neutral isoleucine (1), deprotonated leucine (2), monodeprotonated aspartic acid (3), and neutral valine (4). The crystal structures reveal that the PbII ions are preferably coordinated by oxygen atoms and that the amine group of the amino acids is coordinated only in the case of leucine. The results of the solid‐state NMR spectroscopic experiments are compared to the 3D structures obtained from single‐crystal X‐ray data. The NMR spectroscopic experiments show one, two, one, and four lead sites for the Hile, leu–, Hasp–, and Hval complexes, respectively, in agreement with crystal structures. The application of this method towards the characterization of new Pb compounds, for which no 3D structure is known, is discussed and illustrated with an example where a mechanical mixture of two lead complexes is characterized successfully. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Three‐Component Synthesis of Cryofluorescent 2,4‐Disubstituted 3H‐1,5‐Benzodiazepines – Conformational Control of ­Emission Properties
Authors: Willy Benjamin , Dallos Timea , Rominger Frank , Schönhaber Jan , Müller Thomas J. J.
Published: August 2008

2,4‐Disubstituted benzodiazepines are readily synthesized in good yields from acyl chlorides, terminal alkynes, and benzene‐1,2‐diamines by a consecutive one‐pot, three‐component Sonogashira coupling/Michael addition/cyclocondensation sequence. These diazepines display intense solid‐state fluorescence, but only weak emission in solution at room temperature. The absorption and emission maxima can be controlled by the substitution pattern. Upon cooling, however, the phenomenon of cryofluorescence can be observed. X‐ray structure analysis and temperature‐dependent NMR indicate that freezing out of conformational interconversions is the source of the thermochromicity observed upon UV excitation.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Salt‐Free Synthesis of Tertiary Amines by Ruthenium‐Catalyzed Amination of Alcohols
Authors: Tillack Annegret , Hollmann Dirk , Mevius Kathleen , Michalik Dirk , Bähn Sebastian , Beller Matthias
Published: August 2008

The amination of secondary alcohols to give tertiary amines in the presence of different in situ generated ruthenium catalysts has been investigated in detail. By applying a combination of [Ru3(CO)12] and N‐phenyl‐2‐(dicyclohexylphosphanyl)pyrrole as the catalyst, cyclic amines can be alkylated with different alcohols in high yield, whereas aliphatic amines gave transalkylation side products.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Loss of control over eating in overweight youngsters: The role of anxiety, depression and emotional eating
Authors: Goossens Lien , Braet Caroline , Van Vlierberghe Leen , Mels Saskia
Published: August 2008

The current study investigated loss of control (LC) over eating and the role of anxiety, depression and emotional eating in a sample of both treatment seeking (N = 115) and non‐treatment seeking (N = 73) overweight youngsters (aged 8–18) using a semi‐structured clinical interview and self‐report questionnaires. It was found that treatment seekers reported twice as much LC (40%) compared to non‐treatment seekers (21%). Cross‐sectional prediction models indicated that increased anxiety was associated with emotional eating and LC. Emotional eating tended to mediate the relationship between anxiety and LC. Increased depression was associated with emotional eating but not with LC. Especially overweight treatment seekers turn out to be at risk for LC. Because LC may develop as a result of inadequate coping with negative emotions like anxiety, obesity treatment should focus on teaching more effective coping strategies. Longitudinal research is recommended to further elaborate affect regulation and LC. Copyright © 2008 John Wiley & Sons, Ltd and Eating Disorders Association.
Learning experiences in dance class predict adult eating disturbance
Authors: Annus Agnes , Smith Gregory T.
Published: August 2008

Elite dancers are at increased risk of eating disorders. The authors hypothesized that specific learning about thinness in dance class, rather than simple participation in dance training, tends to be an important aspect of the risk process. Approximately 500 college women reported on their previous dance experiences, their dance‐related learning about thinness, their eating behaviours and attitudes and their thinness expectancies. Results showed that lifetime amount of time spent in dance class was unrelated to adult eating disturbance, women's reports of learning experiences concerning thinness during their dance classes predicted adult disordered eating concurrently, and thinness expectancies appeared to mediate the relationship between learning about thinness and adult eating disturbance. Learning experiences about thinness in dance class seem more important than time spent in dance class when examining the relationship between dance study and eating disorders. Copyright © 2008 John Wiley & Sons, Ltd and Eating Disorders Association.
Timing primate evolution: Lessons from the discordance between molecular and paleontological estimates
Authors: Steiper M. E. , Young N. M.
Published: August 2008

The molecular clock has become an increasingly important tool in evolutionary biology and biological anthropology. Nevertheless, a source of contention with respect to this method is the frequent discordance with fossil‐based estimates of divergence times. The primate radiation is a case in point: Numerous studies have dated the major primate nodes (reviewed in Steiper and Young,1, 2) and there are many instances where molecular and fossil‐based estimates of divergence times differ (Fig. 1). Some investigators have recently focused on phenomena such as stratigraphic dating, the stochastic nature of molecular time estimates, and other sources as potential biases in molecular clock estimates.3, 4 In this paper we do not focus on accuracy or statistical error; rather, we argue that discordance is a predictable phenomenon that provides valuable information about the tempo and mode of primate molecular and morphological evolution. Using this perspective, we reexamine the principal theoretical and methodological factors that lead to discordance between molecular and fossil estimates of the origins of taxa and discuss how a better understanding of these factors can help to improve our understanding of primate evolution.
Disentangling the prefrontal network for rule selection by means of a non‐verbal variant of the Wisconsin Card Sorting Test
Authors: Specht Karsten , Lie Chuh‐Hyoun , Shah Nadim. Jon , Fink Gereon R.
Published: August 2008

This study disentangles the prefrontal network underlying executive functions involved in the Wisconsin Card Sorting Test (WCST). During the WCST, subjects have to perform two key processes: first, they have to derive the correct sorting rule for each trial by trial‐and‐error, and, second, they have to detect when this sorting rule is changed by the investigator. Both cognitive processes constitute key components of the executive system, which is subserved by the prefrontal cortex. For the current fMRI experiment, we developed a non‐verbal variant of the WCST. Subjects were instructed either to respond according to a given sorting rule or to detect the correct sorting rule, like in the original version of the WCST. Data were obtained from 14 healthy male volunteers and analysed using SPM and a random effects model. All conditions activated a fronto‐parietal network, which was generally more active when subjects had to search for the correct sorting rule than when the rule was announced beforehand. Significant differences between these two conditions were seen in the dorsolateral prefrontal cortex (PFC) and the parietal lobe. In addition, the data provided new evidence for the assumption of differentiated roles of the left and right prefrontal cortex. Although the right PFC showed a general involvement in response selection and the execution of goal directed responses, based on given rules, the left PFC was only activated when inductive reasoning and feedback integration was required. Hum Brain Mapp 2009. © 2008 Wiley‐Liss, Inc.
Tumor expressed PTHrP facilitates prostate cancer‐induced osteoblastic lesions
Authors: Liao Jinhui , Li Xin , Koh Amy J. , Berry Janice E. , Thudi Nanda , Rosol Thomas J. , Pienta Kenneth J. , McCauley Laurie K.
Published: August 2008

Expression of parathyroid hormone‐related protein (PTHrP) correlates with prostate cancer skeletal progression; however, the impact of prostate cancer‐derived PTHrP on the microenvironment and osteoblastic lesions in skeletal metastasis has not been completely elucidated. In this study, PTHrP overexpressing prostate cancer clones were stably established by transfection of full length rat PTHrP cDNA. Expression and secretion of PTHrP were verified by western blotting and IRMA assay. PTHrP overexpressing prostate cancer cells had higher growth rates in vitro, and generated larger tumors when inoculated subcutaneously into athymic mice. The impact of tumor‐derived PTHrP on bone was investigated using a vossicle co‐implant model. Histology revealed increased bone mass adjacent to PTHrP overexpressing tumor foci, with increased osteoblastogenesis, osteoclastogenesis and angiogenesis. In vitro analysis demonstrated pro‐osteoclastic and pro‐osteoblastic effects of PTHrP. PTHrP enhanced proliferation of bone marrow stromal cells and early osteoblast differentiation. PTHrP exerted a pro‐angiogenic effect indirectly, as it increased angiogenesis but only in the presence of bone marrow stromal cells. These data suggest PTHrP plays a role in tumorigenesis in prostate cancer, and that PTHrP is a key mediator for communication and interactions between prostate cancer and the bone microenvironment. Prostate cancer‐derived PTHrP is actively involved in osteoblastic skeletal progression. © 2008 Wiley‐Liss, Inc.
A polygenic model with common variants may predict lung adenocarcinoma risk in humans
Authors: Galvan Antonella , Falvella Felicia S. , Spinola Monica , Frullanti Elisa , Leoni Vera P. , Noci Sara , Alonso Maria R. , Zolin Anna , Spada Elena , Milani Silvano , Pastorino Ugo , Incarbone Matteo , Santambrogio Luigi , Neira Anna Gonzalez , Dragani Tommaso A.
Published: August 2008

Genome‐wide screening for genetic loci associated with risk of lung adenocarcinoma (ADCA) was carried out in pooled DNA using the Illumina 300K single‐nucleotide polymorphism (SNP) array, in a joint analysis of 2 Italian case–control series matched by age, gender and smoking habit. The rare allele carrier status of 8 SNPs was associated with a decreased lung ADCA risk [odds ratios (OR): 0.6–0.8]. In a polygenic model characterized by additive and interchangeable effects, individuals carrying 2 to 6 rare alleles at these 8 SNPs showed a significant trend toward a decreased risk of lung ADCA (up to OR of 0.3). These results suggest the relevance of a polygenic model in the modulation of individual risk of lung ADCA in the general population. © 2008 Wiley‐Liss, Inc.
Promoter hypermethylation of CDH13 is a common, early event in human esophageal adenocarcinogenesis and correlates with clinical risk factors
Authors: Jin Zhe , Cheng Yulan , Olaru Alexandru , Kan Takatsugu , Yang Jian , Paun Bogdan , Ito Tetsuo , Hamilton James P. , David Stefan , Agarwal Rachana , Selaru Florin M. , Sato Fumiaki , Abraham John M. , Beer David G. , Mori Yuriko , Shimada Yutaka , Meltzer Stephen J.
Published: August 2008

Although the CDH13 gene has been shown to undergo epigenetic silencing by promoter methylation in many types of tumors, hypermethylation of this gene in Barrett's‐associated esophageal adenocarcinogenesis has not been studied. Two hundred fifty‐nine human esophageal tissues were therefore examined for CDH13 promoter hypermethylation by real‐time methylation‐specific PCR. CDH13 hypermethylation showed discriminative receiver‐operator characteristic curve profiles, sharply demarcating esophageal adenocarcinoma (EAC) from esophageal squamous cell carcinoma (ESCC) and normal esophagus (NE) (p < 0.0001). CDH13 normalized methylation values (NMV) were significantly higher in Barrett's esophagus (BE), dysplastic BE (D) and EAC than in NE (p < 0.0000001). CDH13 hypermethylation frequency was 0% in NE but increased early during neoplastic progression, rising to 70% in BE, 77.5% in D and 76.1% in EAC. Both CDH13 hypermethylation frequency and its mean NMV were significantly higher in BE with than without accompanying EAC. In contrast, only 5 (19.2%) of 26 ESCCs exhibited CDH13 hypermethylation. Furthermore, both CDH13 hypermethylation frequency and its mean NMV were significantly higher in EAC than in ESCC, as well as in BE or D vs. ESCC. Interestingly, mean CDH13 NMV was significantly lower in short‐segment than in long‐segment BE, a known clinical risk factor for neoplastic progression. Similarly, BE segment length was significantly lower in specimens with unmethylated than with methylated CDH13 promoters. 5‐aza‐2′‐deoxycytidine treatment of OE33 EAC and KYSE220 ESCC cells reduced CDH13 methylation and increased CDH13 mRNA expression. These findings suggest that hypermethylation of CDH13 is a common, tissue‐specific event in human EAC, occurs early during BE‐associated neoplastic progression, and correlates with known clinical neoplastic progression risk factors. © 2008 Wiley‐Liss, Inc.
PX‐478, an inhibitor of hypoxia‐inducible factor‐1α, enhances radiosensitivity of prostate carcinoma cells
Authors: Palayoor Sanjeewani T. , Mitchell James B. , Cerna David , DeGraff William , John‐Aryankalayil Molykutty , Coleman C. Norman
Published: August 2008

Overexpression of hypoxia‐inducible factor‐1α (HIF‐1α) in human tumors is associated with poor prognosis and poor outcome to radiation therapy. Inhibition of HIF‐1α is considered as a promising approach in cancer therapy. The purpose of this study was to test the efficacy of a novel HIF‐1α inhibitor PX‐478 as a radiosensitizer under normoxic and hypoxic conditions in vitro. PC3 and DU 145 prostate carcinoma cells were treated with PX‐478 for 20 hr, and HIF‐1α protein level and clonogenic cell survival were determined under normoxia and hypoxia. Effects of PX‐478 on cell cycle distribution and phosphorylation of H2AX histone were evaluated. PX‐478 decreased HIF‐1α protein in PC3 and DU 145 cells. PX‐478 produced cytotoxicity in both cell lines with enhanced toxicity under hypoxia for DU‐145. PX‐478 (20 μmol/L) enhanced the radiosensitivity of PC3 cells irradiated under normoxic and hypoxic condition with enhancement factor (EF) 1.4 and 1.56, respectively. The drug was less effective in inhibiting HIF‐1α and enhancing radiosensitivity of DU 145 cells compared to PC3 cells with EF 1.13 (normoxia) and 1.25 (hypoxia) at 50 μmol/L concentration. PX‐478 induced S/G2M arrest in PC3 but not in DU 145 cells. Treatment of PC3 and DU 145 cells with the drug resulted in phosphorylation of H2AX histone and prolongation of γH2AX expression in the irradiated cells. PX‐478 is now undergoing Phase I clinical trials as an oral agent. Although the precise mechanism of enhancement of radiosensitivity remains to be identified, this study suggests a potential role for PX‐478 as a clinical radiation enhancer. Published 2008 Wiley‐Liss, Inc.
Prognostic evaluation of epidermal fatty acid‐binding protein and calcyphosine, two proteins implicated in endometrial cancer using a proteomic approach
Authors: Li Zhengyu , Huang Canhua , Bai Shujun , Pan Xiaoling , Zhou Rong , Wei Yuquan , Zhao Xia
Published: August 2008

With the aim to translate the discovery from proteomic research into clinical applications, we identified epidermal fatty acid‐binding protein (E‐FABP) and calcyphosine (CAPS) by MALDI‐Q‐TOF MS and validated their overexpressions by immunoblotting. Their expression statuses were examined by immunohistochemistry in 39 normal endometrium, 29 endometrial intraepithelial neoplasia (EIN) and 84 endometrial cancer (EC) cases. We evaluated the correlations to the clinicopathologic characteristics and determined whether these proteins had prognostic significance. Expressions of E‐FABP and CAPS were increased 2.64‐ and 2.18‐fold in EC by immunoblotting. Immunoreactivity of both E‐FABP and CAPS were stronger in EC than in EIN or normal tissues (p < 0.001 and < 0.001). Stronger immunoreactivity of E‐FABP and CAPS were shown to present with poor differentiation (p = 0.032 and 0.001), but no relevance was observed with staging (p = 1.368 and 4.306). Survival analysis indicated that immunoreactivity of CAPS was correlated to poor survival (p = 0.018), but E‐FABP status appeared to be no correlation to the clinical outcome of patients (p = 0.865). Multivariate analysis indicated that CAPS might be an independent prognostic factor for survival in patients with EC (p = 0.008). Results demonstrated the ubiquitous overexpressions of E‐FABP and CAPS in EC and the correlations to the clinicopathologic parameters. CAPS might be a potential prognostic factor for survival in patients with EC. The research pattern from proteomics to clinical specimens would have widespread applications. © 2008 Wiley‐Liss, Inc.
Analysis of peripheral and local anti‐tumor immune response in esophageal cancer patients after NY‐ESO‐1 protein vaccination
Authors: Wada Hisashi , Sato Eiichi , Uenaka Akiko , Isobe Midori , Kawabata Ryohei , Nakamura Yurika , Iwae Shigemichi , Yonezawa Kouichiro , Yamasaki Makoto , Miyata Hiroshi , Doki Yuichiro , Shiku Hiroshi , Jungbluth Achim A. , Ritter Gerd , Murphy Roger , Hoffman Eric W. , Old Lloyd J. , Monden Morito , Nakayama Eiichi
Published: August 2008

NY‐ESO‐1 antigen is a prototype of a class of cancer/testis antigens. We carried out a clinical trial using NY‐ESO‐1 whole protein as a cancer vaccine for 13 advanced cancer patients. We have recently reported that vaccine elicited humoral and cellular immune responses in 9 cancer patients including 4 esophageal cancer patients, and clinical responses were also observed in 4 of 5 evaluable patients. In this study, we analyzed the responses in 8 esophageal cancer patients including 4 newly enrolled patients. Patients were injected subcutaneously at biweekly intervals with NY‐ESO‐1 recombinant protein formulated with cholesterol‐bearing hydrophobized pullulan. Induction of antibody, and CD4 and CD8 T‐cell responses were observed in 7, 7 and 6 patients, respectively, out of 8 patients. 1 PR, 2 SD and 2 mixed clinical responses were observed in 6 evaluable patients. No significant adverse events were observed. Furthermore, we analyzed NY‐ESO‐1 and MHC class I expression and the infiltration of immune cells into tumor samples obtained before and after vaccination from 4 patients by immunohistochemistry. The results showed 2 patients with disappearance of CD4 and CD8 T‐cell infiltration, 1 patient with increase in the number of CD68+ macrophages and 1 patient with tumor antigen loss in the progressive tumors following vaccinations. The induction of NY‐ESO‐1 immunity and some preferable clinical outcomes were observed in esophageal cancer patients by vaccination with NY‐ESO‐1. However, the tumors grew eventually by various mechanisms after vaccination. © 2008 Wiley‐Liss, Inc.
Identification of novel Smad2 and Smad3 associated proteins in response to TGF‐β1
Authors: Brown Kimberly A. , Ham Amy‐Joan L. , Clark Cara N. , Meller Nahum , Law Brian K. , Chytil Anna , Cheng Nikki , Pietenpol Jennifer A. , Moses Harold L.
Published: August 2008

Transforming growth factor‐beta 1 (TGF‐β1) is an important growth inhibitor of epithelial cells and insensitivity to this cytokine results in uncontrolled cell proliferation and can contribute to tumorigenesis. TGF‐β1 signals through the TGF‐β type I and type II receptors, and activates the Smad pathway via phosphorylation of Smad2 and Smad3. Since little is known about the selective activation of Smad2 versus Smad3, we set out to identify novel Smad2 and Smad3 interacting proteins in epithelial cells. A non‐transformed human cell line was transduced with Myc‐His6‐Smad2 or Myc‐His6‐Smad3‐expressing retrovirus and was treated with TGF‐β1. Myc‐His6‐Smad2 or Myc‐His6‐Smad3 was purified by tandem affinity purification, eluates were subject to SDS–PAGE and Colloidal Blue staining, and select protein bands were digested with trypsin. The resulting tryptic peptides were analyzed by liquid chromatography (LC) and tandem mass spectrometry (MS/MS) and the SEQUEST algorithm was employed to identify proteins in the bands. A number of proteins that are known to interact with Smad2 or Smad3 were detected in the eluates. In addition, a number of putative novel Smad2 and Smad3 associated proteins were identified that have functions in cell proliferation, apoptosis, actin cytoskeleton regulation, cell motility, transcription, and Ras or insulin signaling. Specifically, the interaction between Smad2/3 and the Cdc42 guanine nucleotide exchange factor, Zizimin1, was validated by co‐immunoprecipitation. The discovery of these novel Smad2 and/or Smad3 associated proteins may reveal how Smad2 and Smad3 are regulated and/or uncover new functions of Smad2 and Smad3 in TGF‐β1 signaling. J. Cell. Biochem. 105: 596–611, 2008. © 2008 Wiley‐Liss, Inc.
Regulatory expression of Brachyury and Goosecoid in P19 embryonal carcinoma cells
Authors: Nakaya Kohei , Murakami Masaru , Funaba Masayuki
Published: August 2008

Mouse P19 embryonal carcinoma cells can differentiate into various cell types depending on culture conditions. Here we show that the expression of the mesodermal genes Brachyury (Bra) and Goosecoid (Gsc) are under regulatory control in P19 cells. When P19 cells were cultured in a tissue culture dish in the presence of serum, Bra and Gsc were unexpectedly expressed. Expression of Bra and Gsc was greatly reduced with culture time, and expression levels at 144 h of culture were below 25% those at 48 h of culture. Members of the Tgf‐β family such as Activin and Nodal have been known to up‐regulate expression of mesodermal genes. Treatment with SB431542, an Alk4/5/7 inhibitor, decreased Bra and Gsc in a dose‐dependent manner, whereas it induced the expression of the neuroectodermal genes Mash‐1 and Pax‐6. Quantitative RT‐PCR and dsRNAi transfection indicated Nodal as a possible ligand responsible for the regulation of Bra and Gsc. In addition, exogenous Nodal increased expression of Bra and Gsc in a dose‐dependent manner. Serum concentration in culture medium positively related to expression of Nodal, Bra, Gsc, and Cripto, which encodes a membrane‐tethered protein required for Nodal signaling. Addition of the culture supernatant of P19 cells at 144 h of culture to medium decreased expression of these genes. The present study reveals that stimulation and inhibition of the Nodal pathway increases mesodermal genes and neuroectodermal genes, respectively, indicating the importance of control of Nodal and Cripto expression for mesodermal formation and neurogenesis. J. Cell. Biochem. 105: 801–813, 2008. © 2008 Wiley‐Liss, Inc.
Lipopolysaccharide suppresses RANK gene expression in macrophages by down‐regulating PU.1 and MITF
Authors: Ishii Junko , Kitazawa Riko , Mori Kiyoshi , McHugh Kevin P. , Morii Eiichi , Kondo Takeshi , Kitazawa Sohei
Published: August 2008

Receptor activator of NF‐κB (RANK) is a receptor for RANK ligand (RANKL), and signals transduced by RANK–RANKL interaction are prerequisite for the differentiation and activation of osteoclasts. We cloned and characterized a 6‐kb fragment containing the 5′‐flanking region of the mouse RANK gene. A fragment of 1‐kb from the transcription start sites containing four Sp‐1 sites and putative binding sites for MITF, CRE/AP‐1, and PU.1 was ligated to the pGL3‐basic vector, and the promoter activity was confirmed by transfection studies. By electrophoretic gel motility shift assay, both PU.1 and proximal MITF binding site showed specific DNA‐protein binding. Co‐transfection studies with MITF‐ and PU.1‐expression vectors revealed that MITF and PU.1 increased RANK promoter activity three‐ and twofold, respectively, and sixfold synergistically. Taken together, these results show that RANK transcription is positively regulated by both PU.1 and MITF. The effect of lipopolysaccharide (LPS) on RANK gene expression, analyzed by in situ hybridization using mouse bone tissue, showed that LPS decreased RANK transcripts of both precursor and mature osteoclasts. Furthermore, LPS treatment of RAW.264.7 cells decreased their RANK mRNA expression by 70%, mirroring the decrease of PU.1 and MITF mRNA. Short‐term treatment with LPS decreased the promoter activity of pGL3‐WT by 70%. Although LPS has been reported to promote osteoclastogenesis in chronic and local pyogenic inflammation, we speculate that LPS per se may directly suppress RANK expression in the osteoclastic cell lineage by down‐regulating the expression of PU.1 and MITF genes in acute and systemic severe endotoxemia, such as in septic shock. J. Cell. Biochem. 105: 896–904, 2008. © 2008 Wiley‐Liss, Inc.
Helenalin‐mediated post‐transcriptional regulation of p21(Cip1) inhibits 3T3‐L1 preadipocyte proliferation
Authors: Fernandes Karishma M. , Auld Corinth A. , Hopkins Robin G. , Morrison Ron F.
Published: August 2008

We have previously shown that post‐transcriptional mechanisms involving the 26S proteasome regulate the cyclin‐dependent kinase inhibitors (CKIs), p21(Cip1) and p27(Kip1) during preadipocyte proliferation. Earlier studies further demonstrated that the anti‐inflammatory, anti‐carcinogenic phytochemical, helenalin is a potent inhibitor of periodic Skp2 accumulation, an F‐box protein mediating SCF E3 ligase ubiquitylation and degradation of both CKIs during S phase progression. Data presented here demonstrate that helenalin dose‐dependently induced G1 arrest of synchronously replicating 3T3‐L1 preadipocytes. This effect occurred in the absence of discernable indices of cell toxicity or apoptosis under the conditions used in this study. Our results demonstrate that helenalin markedly increased p21 protein accumulation in both density‐arrested and proliferating preadipocytes in a dose‐dependent manner. This increase in p21 protein abundance occurred without change in mRNA transcript demonstrating that post‐transcriptional mechanisms were involved. This notion was further supported by the modest accumulation of polyubiquitylated p21 following treatment with helenalin suggesting that suppression of targeted p21 proteolysis by the 26S proteasome contributed to helenalin‐mediated p21 accumulation. The increase in p21 protein was compartmentalized to the nucleus where p21 is known to inhibit cell cycle progression. Finally, helenalin increased protein–protein interactions between p21 and cyclin‐dependent kinase 2 (Cdk2) which may account in part for the anti‐proliferative effect in 3T3‐L1 preadipocytes. J. Cell. Biochem. 105: 913–921, 2008. © 2008 Wiley‐Liss, Inc.
PhAST: Pharmacophore alignment search tool
Authors: Hähnke Volker , Hofmann Bettina , Grgat Tomislav , Proschak Ewgenij , Steinhilber Dieter , Schneider Gisbert
Published: August 2008

We present a ligand‐based virtual screening technique (PhAST) for rapid hit and lead structure searching in large compound databases. Molecules are represented as strings encoding the distribution of pharmacophoric features on the molecular graph. In contrast to other text‐based methods using SMILES strings, we introduce a new form of text representation that describes the pharmacophore of molecules. This string representation opens the opportunity for revealing functional similarity between molecules by sequence alignment techniques in analogy to homology searching in protein or nucleic acid sequence databases. We favorably compared PhAST with other current ligand‐based virtual screening methods in a retrospective analysis using the BEDROC metric. In a prospective application, PhAST identified two novel inhibitors of 5‐lipoxygenase product formation with minimal experimental effort. This outcome demonstrates the applicability of PhAST to drug discovery projects and provides an innovative concept of sequence‐based compound screening with substantial scaffold hopping potential. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2009
Application of error‐ranked singular value decomposition for the determination of potential‐derived atomic‐centered point charges
Authors: Tan Jeffrey S. , Boerrigter Stephan X. M. , Scaringe Raymond P. , Morris Kenneth R.
Published: August 2008

The present work provides a detailed investigation on the use of singular value decomposition (SVD) to solve the linear least‐squares problem (LLS) for the purposes of obtaining potential‐derived atom‐centered point charges (PD charges) from the ab initio molecular electrostatic potential (VQM). Given the SVD of any PD charge calculation LLS problem, it was concluded that (1) all singular vectors are not necessary to obtain the optimal set of PD charges and (2) the most effective set of singular vectors do not necessarily correspond to those with the largest singular values. It is shown that the efficient use of singular vectors can provide statistically well‐defined PD charges when compared with conventional PD charge calculation methods without sacrificing the agreement with VQM. As can be expected, the methodology outlined here is independent of the algorithm for sampling VQM as well as the basis set used to calculate VQM. An algorithm is provided to select the best set of singular vectors used for optimal PD charge calculations. To minimize the subjective comparisons of different PD charge sets, we also provide an objective criterion for determining if two sets of PD charges are significantly different from one another. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2009
Application of the dressed time‐dependent density functional theory for the excited states of linear polyenes
Authors: Mazur Grzegorz , Włodarczyk Radosław
Published: August 2008

Dressed Time‐Dependent Density Functional Theory (Maitra et al., J Chem Phys 2004, 120, 5932) is applied to selected linear polyenes. Limits of validity of the approximation are briefly discussed. The implementation strategy is described. Results for the 21Bu and 21Ag states of selected linear polyenes are presented and compared with accessible experimental and theoretical results. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2009
Prediction of acidity in acetonitrile solution with COSMO‐RS
Authors: Eckert Frank , Leito Ivo , Kaljurand Ivari , Kütt Agnes , Klamt Andreas , Diedenhofen Michael
Published: August 2008

The COSMO‐RS method, a combination of the quantum chemical dielectric continuum solvation model COSMO with a statistical thermodynamics treatment for realistic solvation simulations, has been used for the prediction of pKa values in acetonitrile. For a variety of 93 organic acids, the directly calculated values of the free energies of dissociation in acetonitrile showed a very good correlation with the pKa values (r2 = 0.97) in acetonitrile, corresponding to a standard deviation of 1.38 pKa units. Thus, we have a prediction method for acetonitrile pKa with the intercept and the slope as the only adjusted parameters. Furthermore, the pKa values of CH acids yielding large anions with delocalized charge can be predicted with a rmse of 1.12 pKa units using the theoretical values of slope and intercept resulting in truly ab initio pKa prediction. In contrast to our previous findings on aqueous acidity predictions the slope of the experimental pKa versus theoretical ΔGdiss was found to match the theoretical value 1/RT ln (10) very well. The predictivity of the presented method is general and is not restricted to certain compound classes. However, a systematic correction of −7.5 kcal mol−1 is required for compounds that do not allow electron‐delocalization in the dissociated anion. The prediction model was tested on a diverse test set of 129 complex multifunctional compounds from various sources, reaching a root mean square deviation of 2.10 pKa units. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2009
Implementation and use of a direct, partially integral‐driven non‐Dyson propagator method for molecular ionization
Authors: Storchi Loriano , Vitillaro Giuseppe , Tarantelli Francesco
Published: August 2008

The Green's function ADC(3) scheme has been for many years a successful method to predict theoretically the ionization (and electron affinity) spectrum of molecules. However, a dramatic enhancement of the method's power has come only recently, with the development of an approximation method to the one‐particle Green's function which does not make direct use of the Dyson equation. In the present work, we present an efficient computer implementation of this novel approach, with first comparative tests demonstrating its enormous computational advantage over the conventional approach. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2009
Who copes well? Obesity‐related coping and its associations with shame, guilt, and weight loss
Authors: Conradt Matthias , Dierk Jan‐Michael , Schlumberger Pia , Rauh Elisabeth , Hebebrand Johannes , Rief Winfried
Published: August 2008

The relationship among weight‐related coping, guilt, and shame was investigated in a sample of 98 obese German individuals over a 6‐month period. In terms of the objectives, the study explored the kind and frequency of typical coping situations in which obese individuals become aware of being obese. Furthermore, the study sought to determine the predictive utility of weight‐related shame and guilt concerning coping responses, and to establish whether there is an association between coping responses and weight change. A longitudinal examination over a 6‐month period was chosen with two measurement points. As typical distressing coping situations, individuals reported mostly negative evaluations through others/self, physical exercise situations, or environmental hazards (mainly shopping for clothes). Weight‐related shame at baseline was a significant negative predictor for problem‐focused engagement coping, whereas weight‐related guilt was a significant positive predictor for problem‐focused engagement strategies and dietary restraint at follow‐up. Although Body Mass Index showed no substantial association with the coping measures, weight loss was accompanied by a substantial drop in problem‐focused disengagement coping (wishful thinking, problem avoidance). Discussion of these findings focuses on the issue of possible effects of weight‐related feelings of guilt and shame on coping behavior, the link between weight loss and disengaging coping strategies, and the possible use of the findings for cognitive–behavioral therapy for obesity. © 2008 Wiley Periodicals, Inc. J Clin Psychol 64:1–16, 2008.