bluuebunny/crossref_metadata_2025 huggingface dataset:
Pentose phosphate cycle oxidative and nonoxidative balance: A new vulnerable target for overcoming drug resistance in cancer
Authors: Ramos‐Montoya Antonio , Lee Wai‐Nang P. , Bassilian Sara , Lim Shu , Trebukhina Raisa V. , Kazhyna Maria V. , Ciudad Carlos J. , Noé Véronique , Centelles Josep J. , Cascante Marta
Published: October 2006

The metabolic network of cancer cells confers adaptive mechanisms against many chemotherapeutic agents, but also presents critical constraints that make the cells vulnerable to perturbation of the network due to drug therapy. To identify these fragilities, combination therapies based on targeting the nucleic acid synthesis metabolic network at multiple points were tested. Results showed that cancer cells overcome single hit strategies through different metabolic network adaptations, demonstrating the robustness of cancer cell metabolism. Analysis of these adaptations also identified the maintenance of pentose phosphate cycle oxidative and nonoxidative balance to be critical for cancer cell survival and vulnerable to chemotherapeutic intervention. The vulnerability of cancer cells to the imbalance on pentose phosphate cycle was demonstrated by phenotypic phase plane analysis. © 2006 Wiley‐Liss, Inc.
Ursodeoxycholic acid modulates histone acetylation and induces differentiation and senescence
Authors: Akare Sandeep , Jean‐Louis Samira , Chen Wemin , Wood Daniel J. , Powell Ashley A. , Martinez Jesse D.
Published: October 2006

Agents that can modulate colonic environment and control dysregulated signaling are being evaluated for their chemopreventive potential in colon cancer. Ursodeoxycholate (UDCA) has shown chemopreventive potential in preclinical and animal models of colon cancer, but the mechanism behind it remains unknown. Here biological effects of UDCA were examined to understand mechanism behind its chemoprevention in colon cancer. Our data suggests that UDCA can suppress growth in a wide variety of cancer cell lines and can induce low level of apoptosis in colon cancer cells. We also found that UDCA treatment induces alteration in morphology, increased cell size, upregulation of cytokeratin 8, 18 and 19 and E‐cadherin, cytokeratin remodeling and accumulation of lipid droplets, suggesting that UDCA induces differentiation in colon carcinoma cells. Our results also suggest significant differences in UDCA and sodium butyrate induced functional differentiation. We also report for the first time that UDCA can induce senescence in colon cancer cells as assessed by flattened, spread out and vacuolated morphology as well as by senescence marker β‐galactosidase staining. We also found that UDCA inhibits the telomerase activity. Surprisingly, we found that UDCA is not a histone deacytylase inhibitor but instead induces hypoacetylation of histones unlike hyperacetylation induced by sodium butyrate. Our results also suggest that, although UDCA induced senescence is p53, p21 and Rb independent, HDAC6 appears to be important in UDCA induced senescence. In summary, our data shows that UDCA modulates chromatin by inducing histone hypoacetylation and induces differentiation and senescence in colon cancer cells. © 2006 Wiley‐Liss, Inc.
Identification and meta‐analysis of a small gene expression signature for the diagnosis of estrogen receptor status in invasive ductal breast cancer
Authors: Schneider Jörg , Ruschhaupt Markus , Buneß Andreas , Asslaber Martin , Regitnig Peter , Zatloukal Kurt , Schippinger Walter , Ploner Ferdinand , Poustka Annemarie , Sültmann Holger
Published: October 2006

In breast cancer, the determination of estrogen receptor (ER) expression is crucial for the decision on therapeutic strategies. Current ER expression analysis is based on immunohistochemical (IHC) staining of ER on formalin fixed tissue sections. However, low levels of ER expression frequently escape detection because of varying sensitivities of routine histopathological laboratories. Moreover, in estimating ER by IHC the receptor protein only is tested instead of the complex underlying ER pathway, which reflects its biological activity. To overcome this limitation, we have used the microarray technology to study 56 samples of invasive ductal carcinoma. We infer a robust and reliable signature of 10 genes, which is associated with ER expression and presumably therapeutically relevant biological processes. In a meta‐analysis, the signature was tested on 3 further independent microarray gene expression data sets, covering different laboratories, array platforms, and clinics. The classification based on the signature showed a very low misclassification rate. In summary, the expression of few genes is sufficient to determine ER status. Future decisions on antiestrogen based therapy in breast cancer could be based on this signature rather than on immunostaining alone. © 2006 Wiley‐Liss, Inc.
Surface modification of polymeric biomaterials: Utilization of cyclodextrins for blood compatibility improvement
Authors: Zhao Xiaobin , Courtney James M.
Published: October 2006

A novel modified polymeric biomaterial surface using cyclodextrins (CDs) for improved blood compatibility was studied. Plasticized poly(vinyl chloride) (PVC‐P) was selected for modification and polyethylene was used as a reference material. The modification was achieved by polymer blending. Fibrinogen and albumin adsorption were utilized as indices for the assessment of the blood compatibility. Surface characterization confirmed that CDs were able to accumulate at the PVC surface and alter the surface properties. The combination of other hydrophilic polymers such as poly(ethylene oxide) (PEO) and PEO/poly(propylene oxide) (PPO) copolymers, such as Pluronic F68 (F68), with CDs were also investigated. These modified materials have a remarkable protein‐resistant surface. The combination of B‐cyclodextrin (B‐CD)/PEO and B‐CD/F68 in certain feeding ratio are synergistic in producing enhanced blood compatibility. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2007
Electron microscopic study of novel threadlike structures on the surfaces of mammalian organs
Authors: Lee Byung‐Cheon , Yoo Jung Sun , Ogay Vyacheslav , Kim Ki Woo , Dobberstein Harald , Soh Kwang‐Sup , Chang Byung‐Soo
Published: October 2006

The ultrastructures of novel threadlike structures (NTSs) and corpuscles on the surfaces of internal organs of rats were investigated using electron microscopy. The samples were studied in situ by using a stereomicroscope and were taken for further morphological analysis. Scanning electron microscope (SEM) images revealed a bundle structure of threadlike tissue, which was composed of several 10‐μm‐thick subducts. The surfaces of the corpuscles were rather coarse and fenestrated. The corpuscles had cucumber‐like shapes with an average length of about 2 mm and a thickness of about 400 μm. Transmission electron microscope (TEM) images disclosed disordered collagen fibers, which formed the extracellular matrix of the threadlike tissue, and immune‐function cells, like macrophages, mast cells, and eosinophils. Sinuses of various diameters, which were thought to be cross‐sections of the lumens of the subducts, were observed in the TEM, cryo‐SEM and focused‐ion‐beam SEM images. These SEM images were obtained for the first time to reveal the detailed structure of the NTSs that were only recently discovered. Microsc. Res. Tech., 2006. © 2006 Wiley‐Liss, Inc.
Effect of estradiol and progesterone on thyroid gland in pigs: A histochemical, stereological, and ultrastructural study
Authors: Sekulić Milka , Šošić‐Jurjević Branka , Filipović Branko , Nestorović Nataša , Negić Nataša , Stojanoski Milica Manojlović , Milošević Verica
Published: October 2006

The cellular and subcellular organization of thyroid follicular cells in peripubertal (6‐month‐old) male pigs treated with estradiol‐dipropionate (Oe) plus progesterone (Pr) in combination on the first postnatal day was studied. A stereological method was used for morphometric determinations of the relative volume densities of the follicular epithelium, colloid and interstitium, and for establishing the epithelial height and index of activation rate. Statisticaly significant differences of the examined parameters between the control and Oe+Pr‐treated groups were determined by Student's t‐test. The subcellular organization of thyroid follicular cells was studied using transmission electron microscopy (TEM). When compared with the control group, in the Oe+Pr‐treated pigs, thyroid follicles possessed a noticeably higher follicular epithelium when compared with the control animals. The observed changes were quantified and comparison between the experimental groups showed that the height, volume density of follicular epithelium, and index of activation rate were significantly (P < 0.05) increased, whereas the relative volume density of the colloid was significantly (P < 0.05) decreased. At the subcellular level the thyroid follicular cells of Oe+Pr‐treated pigs were characterized by increased number of polysomes and dense bodies and extensive endoplasmatic reticulum. It was concluded that a single neonatal treatment with female gonadal steroids exerted a prolonged effect on the pig's thyroid, characterized by increased biosynthesis and reabsorption of the colloid by the follicular cells. Microsc. Res. Tech., 2006. © 2006 Wiley‐Liss, Inc.
Development of a biodegradable alginate carrier system for antibiotics and bone cells
Authors: Ueng Steve W.N. , Lee Mel S. , Lin Song–Shu , Chan Err‐Cheng , Liu Shih‐Jung
Published: October 2006

This study presents a novel biodegradable alginate delivery system for antibiotics and bone cells to treat infected bone defects. About 2 × 107 New Zealand rabbit mesenchymal stem cells (MSCs) and 5 mL vancomycin solution (50 mg/mL) were added to 5 mL of 2.5% (w/v) sodium alginate solution to form biodegradable antibiotic and MSCs alginate beads 3 mm in diameter. The alginate beads were then cultured in an osteogenic medium for 14 days. The profiles of antibiotics released from the alginate beads were evaluated using the method of high performance liquid chromatography (HPLC). The expression of osteogenic genes, including Cbfa1 and osteopontin, in the alginate beads was determined by reverse transcription‐polymerase chain reaction (RT‐PCR) analysis. The alkaline phosphatase activity, calcium level, and mineral deposition of the cultured cells within the alginate beads were assessed. Analytical results demonstrated that the concentrations of vancomycin eluted from the alginate beads were, for 14 days, well above the minimal inhibitory concentration of Staphylococcus aureus. Osteopontin and mRNA of Cbfa1 were detected and increased alkaline phosphatase activity and calcium levels were noted, as was a substantial mineral deposition in cultured MSCs. The PKH 26‐labeled MSCs and vancomycin alginate beads were implanted in rabbit bony cavities for in vivo analysis. Implanted PKH 26‐labeled MSCs were identified in the newly formed bony trabeculae in all specimens at 2 and 4 months after implantation and there was abundant mineral deposition. The results of in vitro study demonstrated sustained elution of vancomycin from the alginate carrier for 14 days and good osteogenic differentiation of cultured MSCs in the alginate carrier matrix. The results of in vivo study demonstrated the implanted MSCs participating in new bone formation. Based on experimental evidence, development of a biodegradable alginate carrier system for antibiotics and bone cells is possible, providing a potential treatment procedure for infected bone defects. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:62–72, 2007
Potential opportunity in the development of new therapeutic agents based on endogenous and exogenous inhibitors of the proprotein convertases
Authors: Bontemps Yannick , Scamuffa Nathalie , Calvo Fabien , Khatib Abdel‐Majid
Published: October 2006

The proprotein convertases (PCs) are responsible for the endoproteolytic processing of various protein precursors (e.g., growth factors, receptors, adhesion molecules, and matrix metalloproteinases) implicated in several diseases such as obesity, diabetes, atherosclerosis, cancer, and Alzheimer disease. The potential clinical and pharmacological role of the PCs has fostered the development of various PC‐inhibitors. In this review we summarized the recent findings on PCs inhibitors, their mode of actions and potential use in the therapy of various diseases. © 2006 Wiley Periodicals, Inc. Med Res Rev, 27, No. 5, 631–648, 2007
Structure and processing relationship for olefin copolymers
Authors: Halász L. , Belina K. , Vorster O.
Published: October 2006

The fractional free volume values were calculated from the group‐contributed equation of state in the case of poly(propylene) and 1‐pentene‐propylene copolymers. The calculated values were compared to those, which were determined from the zero shear viscosity. The fractional free volume is an excellent parameter to convert pressure‐volume‐temperature (PVT) data to viscosity and vica versa. Copyright © 2006 John Wiley & Sons, Ltd.
Data mining for signals in spontaneous reporting databases: proceed with caution
Authors: Stephenson Wendy P. , Hauben Manfred
Published: October 2006

Purpose

To provide commentary and points of caution to consider before incorporating data mining as a routine component of any Pharmacovigilance program, and to stimulate further research aimed at better defining the predictive value of these new tools as well as their incremental value as an adjunct to traditional methods of post‐marketing surveillance.

Methods/Results

Commentary includes review of current data mining methodologies employed and their limitations, caveats to consider in the use of spontaneous reporting databases and caution against over‐confidence in the results of data mining.

Conclusions

Future research should focus on more clearly delineating the limitations of the various quantitative approaches as well as the incremental value that they bring to traditional methods of pharmacovigilance. Copyright © 2006 John Wiley & Sons, Ltd.
New insights into DHFR interactions: Analysis of Pneumocystis carinii and mouse DHFR complexes with NADPH and two highly potent 5‐(ω‐carboxy(alkyloxy) trimethoprim derivatives reveals conformational correlations with activity and novel parallel ring stacking interactions
Authors: Cody Vivian , Pace Jim , Chisum Kim , Rosowsky Andre
Published: October 2006

Structural data are reported for two highly potent antifolates, 2,4‐diamino‐5‐[3′,4′‐dimethoxy‐5′‐(5‐carboxy‐1‐pentynyl)]benzylpyrimidine (PY1011), with 5000‐fold selectivity for Pneumocystis carinii dihydrofolate reductase (pcDHFR), relative to rat liver DHFR, and 2,4‐diamino‐5‐[2‐methoxy‐5‐(4‐carboxybutyloxy)benzyl]pyrimidine (PY957), that has 80‐fold selectivity for pcDHFR. Crystal structures are reported for NADPH ternary complexes with PY957 and pcDHFR, refined to 2.2 Å resolution; with PY1011 and pcDHFR, refined to 2.0 Å resolution; and with PY1011 and mouse DHFR (mDHFR), refined to 2.2 Å resolution. These results reveal that the carboxylate of the ω‐carboxyalkyloxy side chain of these inhibitors form ionic interactions with the conserved Arg in the substrate binding pocket of DHFR. These data suggest that the enhanced inhibitory activity of PY1011 compared with PY957 is, in part, due to the favorable contacts with Phe69 of pcDHFR by the methylene carbons of the inhibitor side chain that are oriented by the triple bond of the 1‐pentynyl side chain. These contacts are not present in the PY957 pcDHFR complex, or in the PY1011 mDHFR complex. In the structure of mDHFR the site of Phe69 in pcDHFR is occupied by Asn64. These data also revealed a preference for an unusual parallel ring stacking interaction between Tyr35 of the active site helix and Phe199 of the C‐terminal β sheet in pcDHFR and by Tyr33 and Phe179 in mDHFR that is independent of bound ligand. A unique His174–His187 parallel ring stacking interaction was also observed only in the structure of pcDHFR. These ring stacking interactions are rarely found in any other protein families and may serve to enhance protein stability. Proteins 2006. © 2006 Wiley‐Liss, Inc.
Aggregating the amyloid Aβ11–25 peptide into a four‐stranded β‐sheet structure
Authors: Boucher Geneviève , Mousseau Normand , Derreumaux Philippe
Published: October 2006

We present a detailed analysis of the structural properties of one monomer of Aβ11–25 as well as of the aggregation mechanisms for four chains of Aβ11–25 using the activation–relaxation technique coupled with a generic energy potential. Starting from a random distribution of these four chains, we find that the system assembles rapidly into a random globular state that evolves into three‐ and four‐stranded antiparallel β‐sheets. The aggregation process is considerably accelerated by the presence of preformed dimers. We also find that the reptation mechanism already identified in shorter peptides plays a significant role here in allowing the structure to reorganize without having to fully dissociate. Proteins 2006. © 2006 Wiley‐Liss, Inc.
DFT and TD‐DFT investigation of IR and UV spectra of solvated molecules: Comparison of two SCRF continuum models
Authors: Preat Julien , Loos Pierre‐François , Assfeld Xavier , Jacquemin Denis , Perpète Eric A.
Published: October 2006

We report the calculation of liquid‐phase infrared (IR) and ultraviolet (UV) spectra in the framework of the solute's response to the reaction field of several solvents. In particular, we compare these two properties for the multipolar expansion model developed in the Nancy continuum model (NCM) and the polarized continuum model (PCM) scheme developed in Pise and Naples. All calculations are carried out at the (TD‐)DFT/6–311G(2d,2p) level of theory. The cavity size used for modeling the solute effects on the IR and UV spectra are examined. To calibrate the solute cavity size, we have investigated the IR spectra of coumarin and of a set of 14 additional solutes of different size and polarity in several dielectrical surroundings. It turns out that: (i) PCM and NCM present an identical behavior when a common cavity is used to calibrate the models; and (ii) for both NCM and PCM models, the IR spectra are highly sensitive to the solute and solvent polarity. The UV/VIS investigation of coumarin derivatives demonstrates that both models provide close estimates of λmax independent of the solute cavity size. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2007
From anisole to 1,2,4,5‐tetramethoxybenzene: Theoretical study of the factors that determine the conformation of methoxy groups on a benzene ring
Authors: Velde Christophe Vande , Bultinck Evi , Tersago Karla , Alsenoy Christian Van , Blockhuys Frank
Published: October 2006

Unhindered ortho‐dimethoxy‐substituted phenyl rings often display a coplanar conformation. A theoretical study of a series of methoxybenzenes consisting of methoxybenzene (anisole), the three dimethoxybenzenes, and 1,2,4,5‐tetramethoxybenzene, at the DFT/B3LYP/6‐311++G** level of theory, allows us to identify the factors influencing the conformational preference and attribute the coplanarity of such methoxy groups to mesomeric effects. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2007
Comment on “The electron‐pair origin of anti‐aromaticity: Spectroscopic manifestations”
Authors: Dufey Florian
Published: October 2006

In the article by Zilberg and Haas, “The Electron‐Pair Origin of Anti‐aromaticity: Spectroscopic Manifestations,” the relative sign of the two Kekulé valence bond functions, R and L, in conjugated cyclic hydrocarbons was discussed. It was proposed that in the ground‐state wave function of aromatic compounds, the two functions contribute with like sign, while in the ground state of anti‐aromatic compounds, the two functions contribute with opposite sign. In this Comment, it is shown that the two functions enter with like sign also into the ground‐state wave function of anti‐aromatic compounds. Furthermore, it was argued that resonance tends to (de)stabilize a symmetric ground‐state geometry in case of the (anti‐)aromatic compounds. The expression derived by Zilberg and Haas for the stabilization energy shows an unusual dependence on the ring size and distortion coordinate. An alternative formula is derived for the stabilization energy, in which the energy depends quadratically on the distortion coordinate. Without further numerical calculations, it is not possible to predict whether this term will (de)stabilize a symmetric geometry of the ground state of (anti‐)aromatic molecules. Rather, we are led to believe that the influence of term in question on the geometric stability may be small, thus not providing the main reason for the geometric distortion of anti‐aromatic compounds. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2007
DFT and local MP2 study of switching process in a pH controllable molecular “shuttle”
Authors: Fomine Serguei , Guadarrama Patricia , Zolotukhin Mikhail
Published: October 2006

A pH controllable molecular “shuttle,” comprising of dibenzo24crown‐8 (DB24C8) macroring bound to a “finger” molecule possessing two different recognition sites has been studied at the density functional theory (DFT) and Møller‐Plesset second‐order (MP2) levels of theory. The calculation confirmed experimental results that translational conformer with DB24C8 located around NH station has the lowest energy, while the conformer with DB24C8 located around NH station shows the highest energy. It has been found that Bpym2+ unit consists of two “substations” separated by an energy barrier of 3–17 kcal/mol depending on the state of the NH–NH station. The translational conformers are stabilized by NH…O, +NH…O, +NCH…OH‐bonds, and π–π stacking with different contributions, depending on the conformer type. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem 2007
Guanidination chemistry for qualitative and quantitative proteomics
Authors: Warwood Stacey , Mohammed Shabaz , Cristea Ileana M. , Evans Caroline , Whetton Anthony D. , Gaskell Simon J.
Published: October 2006

The application of guanidination chemistry, the conversion of lysine into homoarginine residues, is used to illustrate several important general considerations relating to the use of differential isotope labelling for relative quantification in proteomics. The derivatisation procedure has been optimised for automation using a liquid handling station designed for proteomics. Automated application of the procedure to the analysis of in‐gel tryptic digests of multiple spots from the two‐dimensional gel electrophoretic (2DE) analysis of proteins from the FDCP‐mix cell line shows near‐universal improvement in protein identification as a result of derivatisation. This chemistry has been extended for relative quantification, applicable to matrix‐assisted laser desorption/ionisation mass spectrometry (MALDI‐MS) and also tandem mass spectrometry (MS/MS). It provides a robust method for the quantitative comparison of two samples that have been separated by 2DE. A peptide pair may display poor detection during MS analysis, causing their reliable relative quantification to be difficult. In such circumstances, the additional selectivity of detection provided by MS/MS can substantiate identification and allow relative quantification of these species via product ion signal ratios. Copyright © 2006 John Wiley & Sons, Ltd.
Effect of thermal processing on the flavonols rutin and quercetin
Authors: Buchner Nadja , Krumbein Angelika , Rohn Sascha , Kroh Lothar W.
Published: October 2006

The current research involves the study of the thermal treatment of quercetin and rutin in an aqueous model system (cooking). These substances were heated and their degradation was followed by high‐performance liquid chromatography/diode‐array detection (HPLC/DAD). The influence of pH and the involvement of oxygen in the degradation were studied. HPLC/electrospray ionization multi‐stage mass spectrometry (ESI‐MSn) was used for the structural characterization of the compounds produced. The influence of the degradation of the phenolic compounds on their antioxidant properties was elucidated by a electron spin resonance (ESR) spectrometry study of the reaction samples mixed with the stabilized radical, Fremy's salt. Strong degradation of the model substances took place under weak basic and oxidative conditions. Quercetin showed the most intense degradation. Protocatechuic acid could be identified as a cleavage reaction product by analyzing its retention time and molar mass during the degradation of quercetin. The structure of a second cleavage product could be identified on the basis of ESI‐MSn fragmentation data. Also, several structures for reaction products of oxidized quercetin are suggested. The ESR analysis showed a decrease in the antioxidant activity of the reaction samples after heat treatment in aqueous solution. Copyright © 2006 John Wiley & Sons, Ltd.
Coaxial multi‐electrode cell (‘O‐trap’) for high‐sensitivity detection at a multiple frequency in Fourier transform ion cyclotron resonance mass spectrometry: main design and modeling results
Authors: Misharin Alexander S. , Zubarev Roman A.
Published: October 2006

Separation of the functions of ion excitation and detection between different cell compartments allows for implementation of excitation and detection techniques unattainable in a single compartment of the conventional ion cyclotron resonance (ICR) cell. In particular, multi‐electrode detection at a multiple of the main cyclotron frequency can be utilized without the loss of sensitivity and other negative effects. The new O‐trap designed exclusively for ion detection adds an additional, internal coaxial cylinder around which ions with excited cyclotron orbits rotate. Comparison of simulated performance characteristics of the new O‐trap with those of the same‐size conventional cylindrical cell shows that the O‐trap can provide higher sensitivity and ion capacity. Multiplexing of the O‐traps can further increase the analysis speed. Future efforts will be aimed at building and testing experimentally the coaxial O‐trap, including optimization of the method of ion transfer between the compartments of the cell. Copyright © 2006 John Wiley & Sons, Ltd.
Transcriptional activation of the proapoptotic bik gene by E2F proteins in cancer cells
Authors: Real Pedro J. , Sanz Cristina , Gutierrez Olga , Pipaon Carlos , Zubiaga Ana M. , Fernandez-Luna Jose L.
Published: October 2006

BH3‐only proteins are required for execution of apoptotic cell death. We have found that one of these proteins, Bik, is strongly induced in cancer cells treated with chemotherapeutic agents. Furthermore, we showed that chemotherapy‐induced expression of bik is independent of p53. Consistent with its pro‐apoptotic activity, blockade of bik expression reduces the adriamycin‐mediated apoptotic cell death. We also found that the bik gene is transcriptionally activated by E2F proteins. Consistently, adriamycin induces the E2F‐bik pathway. In addition, E2Fs transactivate bik by a p53‐independent mechanism. Thus, our data indicate that transcriptional regulation of bik contributes to the efficient apoptotic response to chemotherapeutic agents.
A novel analytical method for in vivo phosphate tracking
Authors: Gu Hong , Lalonde Sylvie , Okumoto Sakiko , Looger Loren L. , Scharff-Poulsen Anne Marie , Grossman Arthur R. , Kossmann Jens , Jakobsen Iver , Frommer Wolf B.
Published: October 2006

Genetically‐encoded fluorescence resonance energy transfer (FRET) sensors for phosphate (Pi) (FLIPPi) were engineered by fusing a predicted Synechococcus phosphate‐binding protein (PiBP) to eCFP and Venus. Purified fluorescent indicator protein for inorganic phosphate (FLIPPi), in which the fluorophores are attached to the same PiBP lobe, shows Pi‐dependent increases in FRET efficiency. FLIPPi affinity mutants cover Pi changes over eight orders of magnitude. COS‐7 cells co‐expressing a low‐affinity FLIPPi and a Na+/Pi co‐transporter exhibited FRET changes when perfused with 100 μM Pi, demonstrating concentrative Pi uptake by PiT2. FLIPPi sensors are suitable for real‐time monitoring of Pi metabolism in living cells, providing a new tool for fluxomics, analysis of pathophysiology or changes of Pi during cell migration.
Caspase‐mediated changes in Sir2α during apoptosis
Authors: Ohsawa Shizue , Miura Masayuki
Published: October 2006

Silent information regulator 2 (Sir2) is an NAD+‐dependent histone deacetylase that establishes repressive chromatin status and extends the life span of both budding yeast and the nematode worm Caenorhabditis elegans. There is growing evidence that its mammalian homologue Sir2α protects cells from stress‐induced apoptosis. We report here that mammalian Sir2α was directly cleaved by both initiator and executioner caspases, and relocated from the nucleus to the cytoplasm in apoptotic cells. These alterations of Sir2α were largely inhibited by a caspase‐9 dominant‐negative mutant or Bcl‐xL. Our results indicate that Sir2α undergoes dynamic changes in caspase‐dependent manner during apoptosis.
Regulation of Stat3 transcriptional activity by the conserved LPMSP motif for OSM and IL‐6 signaling
Authors: Sun Wei , Snyder Marylynn , Levy David E. , Zhang J. Jillian
Published: October 2006

To achieve maximal transcriptional activity in response to gp130 cytokines, Serine‐727 (Ser‐727) of Stat3 is phosphorylated. Ser‐727 resides in the LPMSP motif, the only conserved sequence among the transcription activation domains of several STATs. We show here that in addition to Ser‐727, other residues in this LPMSP motif are also required for Stat3 activity in response to cytokine signaling through regulation of Ser‐727 phosphorylation and recruitment of the transcription co‐activator CBP/p300 to the promoters of Stat3‐target genes for transcription activation. Hence, we have demonstrated a critical role for the whole conserved LPMSP motif in JAK‐STAT signaling.
Les instruments de la politique énergétique: analyse comparée du Canada et des États-Unis
Authors: Varone Frédéric
Published: October 2006

This study tests explanations of the choice of policy instruments. The comparative analysis of the Canadian and United States energy policies for the period 1973-1996 concludes that the choice of a policy instrument is a function of (1) whether the degree of constraint involved is consistent with the ideological predisposition of the party in power, (2) whether the agency needed to implement the instrument already exists, thus reducing costs, (3) whether a policy transfer from other jurisdictions is possible or whether policy harmonization is required, and (4) whether the target groups affected by the use of the instrument are likely to oppose its use.
Women as Wives, Servants and Slaves: Rethinking the Public/Private Divide
Authors: Arneil Barbara
Published: October 2006

Critiques of the public/private divide in Western political thought do not go far enough in analyzing the full range and character of relations in the private sphere as demonstrated in this article, which analyzes John Locke's theorisation about the relative authority of wives, servants and slaves. A third-wave feminist analysis is used to illustrate the theoretical relevance of group-based identities that, far from having a uniform relation to the political power afforded to free (male) citizens, are hierarchically stratified. Thus it is demonstrated that a basic problem within second-wave feminist analysis of Lockean, and more broadly defined liberal thought, is the tendency to categorize women as ''wives'' of free citizens, and not to analyze adequately other dimensions of identity, thereby ignoring the explicit divisions and hierarchy among different groups of women in one of the earliest accounts of the private sphere in liberal theory.
Culture and the Courts: A New Direction in Canadian Jurisprudence on Aboriginal Rights?
Authors: Murphy Michael
Published: October 2006

This article explores the implications of changes in Canadian Supreme Court jurisprudence on Aboriginal rights since the 1990s. While recognizing the Court's valuable contributions in the period from Calder to Sparrow, the author argues that the 1996 Van der Peet decision deals a serious blow to the legal status of Aboriginal rights, particularly the right to self-government. The standard of legal recognition established in Van der Peet constitutes a decided step back from the Court's prior jurisprudence, and is insufficient as a means of securing its stated ends: the survival and well-being of Aboriginal communities and cultures. The author concludes by arguing that the Court can repair the recent damage it has done to Aboriginal rights by revisiting the concept of the quasinational status granted to Aboriginal peoples within the context of the sui generis Crown-Aboriginal relationship.
Double Identities: Aboriginal Policy Agencies in Ontario and British Columbia
Authors: Malloy Jonathan
Published: October 2006

This article argues that provincial government units for Aboriginal affairs in Ontario and British Columbia have ''double identities'' stemming from contradictory mandates anchored in two different policy communities. Aboriginal policy agencies act as Crown negotiators with Aboriginal nations over land claims and self-government, but are also responsible for co-ordinating government policies affecting Aboriginals. Consequently, they interact with two different policy communities. One involves economic and resource ministries, which engage in a pressure pluralist relationship with Aboriginal groups. The second involves social policy ministries who engage in more clientele pluralist relationships with Aboriginals. Consequently, Aboriginal policy agencies display different identities and play different and sometimes contradictory roles. These ''double identities'' illustrate the complexity and contradictions of provincial-Aboriginal relations in Canada.
GOING AGAINST THE GRAIN IN SICILIAN GREEK ECONOMICS
Authors: DE ANGELIS FRANCO
Published: October 2006

On his recent retirement from the chair of classical archaeology in Cambridge University, Anthony Snodgrass reflected on the state of the subject, wondering whether a paradigm shift has occurred. Snodgrass assesses various matters, including, for our purposes, how archaeological approaches to ancient literary sources have changed. His comments deserve quotation in full:

…Classical archaeology is often stigmatized, by its many critics, as being ‘text-driven’ … [in] that the subject takes its orientation from, and adapts its whole narrative to, the lead given by the literary sources. Thus the archaeology of Roman Britain has been built around Tacitus' narrative of conquest; the study of Greek art around the text of the Elder Pliny; the archaeology of fifth-century Athens around the narratives supplied by Herodotus, Thucydides and Xenophon; that of Republican Rome similarly around those of Livy and Diodorus; that of Sicily again around Thucydides; and most notoriously, that of Aegean prehistory and protohistory around Homer…. But there is a deeper level still. Traditional Classical archaeology is stated…to have directed its energies at those aspects of the ancient world on which the written sources, taken as a whole, throw light. Thus, on urban but not on rural life; on public and civic, but not on domestic activity; on periods seen as historically important, but not on the obscurer ones; on the permanent physical manifestations of religion, but not on the temporary ones – sacrifice, patterns of dedication, ritual meals, pilgrimage; on the artefacts interred in burials, but not on burial itself; on the historically prominent states – in Greece, Athens and Sparta – but not on what has recently been called ‘the Third Greece’…
II Channels of Communication
Authors: Steel Catherine
Published: October 2006

The oral dimension to classical literature as a whole has, rightly, become an object of increasing interest to interpreters. The process of composition of any text usually involved a spoken element; public or private readings could be a medium by which a text was disseminated; and individual reading could involve audible speech, or having another person read aloud. All Roman literature involves some oral dimension. Within this broad framework, however, oratory occupies a distinctive space. A speech is prepared for a specific time and place, to be directed at a specific audience and, in the case of forensic and deliberative oratory, with the aim of securing a specific outcome. Moreover, this first performance is, logically, oral and does not imply the existence of a written text; indeed, there was a strong convention within ancient rhetoric that speeches were delivered from memory, and even though written texts might well feature in preparation, orators would often find themselves in situations where improvisation was necessary. The sense of being created for a particular time and place is a characteristic which oratory shares with drama but, unlike drama, subsequent performances in a similar manner are difficult to envisage. Plays in both Greece and Rome were revived after the festival for which they had been initially composed; but the circumstances in front of the Roman people, in the Senate, or in a court which demanded a speech would never be repeated.
III The Practising Orator
Authors: Steel Catherine
Published: October 2006

We have already seen how public speaking was central, during the Republican period, to the operation of the Roman state; and how, despite radical political change between Republic and Empire, oratory retained its position as a key skill for the politically active elite. The importance of oratory made it, in turn, both the vehicle of and the focus for sustained critiques of the behaviour and values of Rome in general and the elite in particular. In this chapter I turn to the figure of the orator and consider how the expectations concerning his behaviour are set up. Technical works on rhetoric, anecdotes about individual orators and surviving oratorical texts can supplement surviving texts of speeches in the task of establishing what the Romans thought their speakers should do and be and how they criticised those who failed to meet these criteria.
Conclusion
Authors: Steel Catherine
Published: October 2006

On the front cover of this book is an image of a coin minted in 45 B.C. It shows the speaker's platform (rostra) in the Roman forum, decorated with the beaks of ships captured from the Antiates in 341 B.C., and the tribunes' bench. Above the image is the name of the coiner: ‘PALIKANUS’. It is an appropriate image for a book which has been concerned above all with oratory as a series of occasions which happened at specific times and places and which derived its importance from the fact of performance. However, from that perspective any image of the rostra would be suitable.
INFLUENCE OF HEIGHT ON ATTAINED LEVEL OF EDUCATION IN MALES AT 19 YEARS OF AGE
Authors: SZKLARSKA ALICJA , KOZIEŁ SŁAWOMIR , BIELICKI TADEUSZ , MALINA ROBERT M.
Published: October 2006

In this study it is hypothesized that taller individuals are more likely to move up the scale of educational attainment compared with shorter individuals from the same social background. Three national cohorts of 19-year-old males were considered: 29,464 born in 1967 and surveyed in 1986, 31,062 born in 1976 and surveyed in 1995, and 30,851 born in 1982 and surveyed in 2001. Four social variables were used to describe the social background of each conscript in the three surveys: degree of urbanization, family size, and parental and maternal educational status. The educational status of each conscript was classified into two groups: (1) those who were secondary school students or graduates, or who had entered college, and (2) those who had completed their education at the primary school level or who had gone to a basic trade school. Multiple binomial logistic regressions were used to estimate the relative risk of achieving higher educational status by 19-year-old males relative to height and the four social factors. Consistently across the three cohorts the odd ratios (ORs) indicate that height exerts an independent and significant effect on the attained level of education at the age of 19 years in males (1986: OR=1·24, p<0·001; 1995: OR=1·24, p<0·001; 2001: OR=1·20, p<0·001). Two possible, not mutually exclusive, selective mechanisms are postulated and discussed: ‘passive’ and ‘active’ action.
Programmed cell death in African trypanosomes
Authors: WELBURN S. C. , MACLEOD E. , FIGARELLA K. , DUZENSKO M.
Published: October 2006

Until recently it had generally been assumed that apoptosis and other forms of programmed cell death evolved during evolution of the metazoans to regulate growth and development in these multicellular organisms. However, recent research is adding strength to the original phenotypic observations described almost a decade ago which indicated that some parasitic protozoa may have evolved a cell death pathway analogous to the process described as apoptosis in metazoa. Here we explore the implications of a programmed cell death pathway in the African tsetse-transmitted trypanosomes.
Neutrophils, apoptosis and phagocytic clearance: an innate sequence of cellular responses regulating intramacrophagic parasite infections
Authors: RIBEIRO-GOMES F. L. , SILVA M. T. , DOSREIS G. A.
Published: October 2006

In complex organisms, apoptosis is a constitutive cell death process that is involved in physiological regulation of cell numbers and that can also be induced in the course of inflammatory and immune responses. Neutrophils are among the first cells recruited during inflammation. Neutrophils constitutively die by apoptosis at inflamed sites, and are ingested by macrophages. Recent studies investigated how phagocytic clearance of senescent neutrophils influences the survival of intracellular protozoan parasites that have been phagocytosed by, or have invaded phagocytes. The results indicate that neutrophil clearance plays an unexpected role in regulation of intramacrophagic protozoan parasite infection.
Autism spectrum disorder and psychopathy: shared cognitive underpinnings or double hit?
Authors: ROGERS JOHN , VIDING ESSI , JAMES BLAIR R. , FRITH UTA , HAPPÉ FRANCESCA
Published: October 2006

Background. We measured psychopathic traits in boys with autism spectrum disorder (ASD) selected for difficult and aggressive behaviour. We asked (i) whether psychopathic tendencies can be measured in ASD independent of the severity of autistic behaviour; (ii) whether individuals with ASD with callous–unemotional (CU) traits differ in their cognitive profile from those without such traits; and (iii) how the cognitive data from this study compare with previous data of youngsters with psychopathic tendencies.

Method. Twenty-eight ASD boys were rated on psychopathic tendencies, autistic traits and a range of cognitive measures assessing mentalizing ability, executive functions, emotion recognition and ability to make moral–conventional distinction.

Results. Our results indicate that psychopathic tendencies are not related to severity of ASD. In addition, such tendencies do not seem to be related to core autistic cognitive deficits, specifically in ‘mind-reading’ or executive function. Boys with co-occurring ASD and CU tendencies share some behaviours and aspects of cognitive profile with boys who have psychopathic tendencies alone.

Conclusions. Callous/psychopathic acts in a small number of individuals with ASD probably reflect a ‘double hit’ involving an additional impairment of empathic response to distress cues, which is not part and parcel of ASD itself.
Neural correlates of enhanced working-memory performance in dissociative disorder: a functional MRI study
Authors: ELZINGA BERNET M. , ARDON ANGELIQUE M. , HEIJNIS MAAIKE K. , De RUITER MICHIEL B. , VAN DYCK RICHARD , VELTMAN DICK J.
Published: October 2006

Background. Memory functioning has been highlighted as a central issue in pathological dissociation. In non-pathological dissociation, evidence for enhanced working memory has been found, together with greater task-load related activity. So far, no imaging studies have investigated working memory in dissociative patients.

Method. To assess working memory in dissociative patients functional magnetic resonance imaging was used during performance of a parametric, verbal working-memory task in patients with a dissociative disorder (n=16) and healthy controls (n=16).

Results. Imaging data showed that both groups activated brain regions typically involved in working memory, i.e. anterior, dorsolateral and ventrolateral prefrontal cortex (PFC), and parietal cortex. Dissociative patients showed more activation in these areas, particularly in the left anterior PFC, dorsolateral PFC and parietal cortex. In line with these findings, patients made fewer errors with increasing task load compared to controls, despite the fact that they felt more anxious and less concentrated during task performance.

Conclusions. These results extend findings in non-pathological high dissociative individuals, suggesting that trait dissociation is associated with enhanced working-memory capacities. This may distinguish dissociative patients from patients with post-traumatic stress disorder, who are generally characterized by impaired working memory.
Medical Borders: Historical, Political, and Cultural Analyses
Authors: Davidovitch Nadav , Zalashik Rakefet
Published: October 2006

Scientific medicine carries within it an inherent contradiction. On the one hand, given its general scientific inquiry into health and disease, their conditions, etiologies, and treatments, it makes a claim for universality. To justify this claim, at different times and in different places, scientific medicine has prioritized techniques such as the medical gaze and autopsies to assure its diagnoses; it has applied numerical methods in order to have a better grasp of diseases and their possible treatments; it has used laboratory analyses in order to understand life at its molecular level; and more recently it has introduced Randomized Clinical Trials (RCT) in order to generalize clinical treatments. On the other hand, contrary to its universalistic claims, scientific medicine sets up and reifies boundaries. It creates distinctions between the healthy and the sick and defines categories, such as gender and race, that have deep political and social meanings.
“In This Miserable Spot Called Quarantine”: The Healthy and Unhealthy in Nineteenth Century Australian and Pacific Quarantine Stations
Authors: Maglen Krista
Published: October 2006

Argument

By examining sources created by people who were detained or employed at the quarantine stations of Australia and the Western Pacific, this article illuminates aspects of the history of disease control that cannot be observed in other source material. Most research examining the history of maritime quarantine has tended to rely on the records of official and government agencies. As a result, discussion has largely been confined to government policy and larger issues of the political, economic, and social consequences of maritime disease control. This article contributes to the historiography by examining personal sources that show how quarantine policy and practice were experienced from the perspective of its participants. They reveal the experiences of otherwise obscured healthy detainees and illuminate agency among quarantined individuals that cannot be observed without these sources.