bluuebunny/crossref_metadata_2025 huggingface dataset:
Chitosaneous hydrogel beads for immobilizing neutral protease for application in the preparation of low molecular weight chitosan and chito‐oligomers
Authors: Li Jin , Du Yumin , Sun Liping , Liang Hongbo , Feng Tao , Wei Yuan'an , Yao Pinjia
Published: June 2006

Enzyme hydrolysis with immobilized neutral protease was carried out to produce low molecular weight chitosan (LMWC) and chito‐oligomers. Neutral protease was immobilized on (CS), carboxymethyl chitosan (CMCS), and N‐succinyl chitosan (NSCS) hydrogel beads. The properties of free and immobilized neutral proteases on chitosaneous hydrogel beads were investigated and compared. Immobilization enhanced enzyme stability against changes in pH and temperature. When the three different enzyme supports were compared, the neutral protease immobilized on CS hydrogel beads had the highest thermal stability and storage stability, and the enzyme immobilized on NSCS hydrogel beads had the highest activity compared to those immobilized on the other supports, despite its lower protein loading. Immobilized neutral protease on all the three supports had a higher Km (Michaelis‐Menten constant) than free enzyme. The Vmax (maximum reaction velocity) value of neutral protease immobilized on CS hydrogel beads was lower than the free enzyme, whereas the Vmax values of enzyme immobilized on CMCS and NSCS hydrogel beads were higher than that of the free enzyme. Immobilized neutral protease on CS, CMCS, and NSCS hydrogel beads retained 70.4, 78.2, and 82.5% of its initial activity after 10 batch hydrolytic cycles. The activation energy decreased for the immobilization of neutral protease on chitosaneous hydrogel beads. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 3743–3750, 2006
Effects of hydrophobic interaction on rheological behavior and microstructure of carboxylated core‐shell latex suspension
Authors: Nakamura Hiroshi , Tachi Kazuyuki
Published: June 2006

We have investigated the effects of hydrophobic interactions on the rheological behavior and microstructure of suspension of carboxylated core‐shell latex particles with changing hydrophobicity of shell polymer and suspending medium. The carboxylated core‐shell latex particles formed lattice‐like microstructures in aqueous suspension with dissociation of carboxyl groups. With increasing hydrophobicity of the shell polymer, the interparticle distance ξ in the microstructure decreased. However, ξ increased with increasing hydrophobicity of the suspending medium. The effect of hydrophobic interaction on ξ was explained by the steric stabilization theory for particles with grafted polymer on the surface. As the carboxylated core‐shell latex particles overlapped each other in the microstructure, an attractive force was generated between the particles in aqueous suspension. With increasing hydrophobicity of the shell, the attractive force increased, but with increasing hydrophobicity of the suspending medium, the attractive force decreased. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 4153–4158, 2006
Preparation, morphology, and properties of multilamellar barrier materials based on blends of high‐density polyethylene and copolyester
Authors: Cui Xiuguo , Wang Xiaodong
Published: June 2006

The multilamellar barrier materials based on the blends of high‐density polyethylene (HDPE) and copolyester (PETG) were prepared via melt extrusion, and poly(ethylene‐co‐acrylic acid) (EAA) as a compatibilizer was incorporated into the blends. A systematic investigation was carried out, with regard to morphology and properties. Scanning electron microscopy observation displayed the laminar morphology for the blends with the whole compositions, and the thinner laminas of the PETG phase formed in the HDPE matrix by incorporating EAA into the blends. In addition, the number and the size of the laminas of the dispersed phases were also dependant on the die temperature and screw speed, respectively. Evaluation of the mechanical properties demonstrated that incorporation of the EAA resulted in an improvement of the mechanical properties. These behaviors are attributed mainly to better adhesion and compatibility between HDPE and PETG, which has been confirmed by thermal analysis and the rheological properties. On the basis of these premises, it is reasonable to suggest that the improved barrier properties of the ternary blends with increasing concentration of the EAA be attributed to both the increase in the number of the laminas of the PETG and the decrease in their thickness, which prohibits the organic solvent molecules from entering into and permeating through the amorphous regions of the blends. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 3791–3799, 2006
Polymerization of norbornene using bis(β‐ketoamino)nickel(II)/MAO catalytic systems
Authors: He Xiaohui , Wu Qing
Published: June 2006

The polymerizations of norbornene were investigated using a series of bis(β‐ketoamino)nickel(II) complexes(1–6) in combination with methylaluminoxane (MAO) in toluene solution. The effects of catalyst structure, Al/Ni molar ratio, reaction temperature, and reaction time on catalytic activity and molecular weight of the polynorbornene were examined in detail. The electronic effect of the substituent around the imino group in the ligand is stronger than the steric bulk one on the polymerization activities, and the activities are in the order of 1 > 2 > 4 > 5 > 6 > 3. The obtained polynorbornenes were characterized by means of 1H‐NMR, 13C‐NMR, FTIR, TG, and WAXD techniques. The analyses results of polymers' structures and properties indicate that the polymerization reaction of norbornene runs in vinyl‐addition polymerization mode. The obtained polynorbornene was confirmed to be vinyl‐type and atactic polymers and showed good thermostability (Tdec > 458°C) and were noncrystalline but had short‐range order. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 4172–4180, 2006
Preparation of polyacrylate‐clay nanocomposites by in‐situ polymerization and heterocoagulation
Authors: Xu Yijin , Brittain William J.
Published: June 2006

Polyacrylate‐clay nanocomposites were prepared by an in situ polymerization method followed by heterocoagulation. In the heterocoagulation method, a cationic polyacrylate emulsion was prepared by emulsion polymerization using a cationic initiator in the presence/absence of free surfactant, cetyl trimethylammonium bromide (CTABr), followed by mixing with an aqueous clay slurry. WAXD results and TEM images suggest that morphologies of these nanocomposites depend on preparation method, mixing method, and the amount of free surfactant. TG‐DTG analyses demonstrate the improvement in thermal stability of these nanocomposites, while DSC results indicate no significant changes in glass transition temperature of these nanocomposites. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 3850–3855, 2006
Control of biodegradability of poly(3‐hydroxybutyric acid) film with grafting acrylic acid and thermal remolding
Authors: Wada Yuki , Mitomo Hiroshi , Kasuya Ken‐Ichi , Nagasawa Naotsugu , Seko Noriaki , Katakai Akio , Tamada Masao
Published: June 2006

Radiation‐induced graft polymerization of acrylic acid (AAc) on poly(3‐hydroxybutyric acid) (PHB) film was carried out and the resulting film was thermally‐remolded. The PHB films grafted with AAc (PHB‐g‐AAc) having a degree of grafting higher than 5% completely lost the enzymatic degradability. The enzymatic degradability of the grafted film was recovered by thermal remolding. The highest enzymatic degradation rate was observed at degree of grafting of 10% after thermal remolding. The PHB‐g‐AAc films and thermally‐remolded PHB‐g‐AAc films were characterized by contact angle and differential scanning calorimetry. The enzymatic degradability of PHB‐g‐AAc films was lost by the grafted AAc, which covered the surface of PHB film. The acceleration of enzymatic degradation in the remolded PHB‐g‐AAc films was mainly caused by decrease of crystallinity of PHB by dispread of grafted AAc during thermal remolding. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 3856–3861, 2006
Regulation of JNK by MKK‐7 in fibroblast‐like synoviocytes
Authors: Inoue Tomoyuki , Hammaker Deepa , Boyle David L. , Firestein Gary S.
Published: June 2006

Objective

JNK regulates matrix metalloproteinase (MMP) gene expression and joint destruction in rheumatoid arthritis (RA). Previous studies demonstrated that the 2 upstream MAPK kinases (MKK‐4 and MKK‐7) are phosphorylated in RA synovium and form a complex with JNK in fibroblast‐like synoviocytes (FLS). However, the functional hierarchy of MKK‐4 and MKK‐7 in FLS has not been determined. We determined the relative contributions of these MKKs by evaluating the effect of MKK‐4 and MKK‐7 gene knockdown in cultured FLS.

Methods

FLS were transfected with MKK‐4 and/or MKK‐7 small interfering RNA, and protein levels were determined by immunoblotting. After stimulation with interleukin‐1β (IL‐1β), tumor necrosis factor α (TNFα), or anisomycin, kinase function was determined by in vitro kinase assay. Activator protein 1 (AP‐1) binding and transcriptional activity were determined by electrophoretic mobility shift assay and AP‐1–luciferase promoter assay, respectively. MMP‐3 expression was determined by enzyme‐linked immunosorbent assay and quantitative polymerase chain reaction.

Results

IL‐1β–induced JNK phosphorylation was dependent on MKK‐7 but not on MKK‐4; however, anisomycin‐activated JNK required both kinases. In vitro kinase assay demonstrated that IL‐1β– or TNFα‐induced JNK activity was only MKK‐7 dependent, while anisomycin‐activated JNK was both MKK‐4 and MKK‐7 dependent. IL‐1β–induced AP‐1 binding activity and AP‐1–driven gene expression were strictly MKK‐7 dependent. Finally, MMP‐3 production only required MKK‐7, and there was no effect of MKK‐4 deficiency.

Conclusion

These data indicate that only MKK‐7 is required for JNK activation in FLS after cytokine stimulation; however, other forms of cellular stress utilize MKK‐4. Thus, JNK function might be modulated by targeting MKK‐7 to suppress cytokine‐mediated FLS activation while leaving other stress responses intact.
Differential survival of leukocyte subsets mediated by synovial, bone marrow, and skin fibroblasts: Site‐specific versus activation‐dependent survival of T cells and neutrophils
Authors: Filer Andrew , Parsonage Greg , Smith Emily , Osborne Chloe , Thomas Andrew M. C. , Curnow S. John , Rainger G. Ed , Raza Karim , Nash Gerard B. , Lord Janet , Salmon Mike , Buckley Christopher D.
Published: June 2006

Objective

Synovial fibroblasts share a number of phenotype markers with fibroblasts derived from bone marrow. In this study we investigated the role of matched fibroblasts obtained from 3 different sources (bone marrow, synovium, and skin) to test the hypothesis that synovial fibroblasts share similarities with bone marrow–derived fibroblasts in terms of their ability to support survival of T cells and neutrophils.

Methods

Matched synovial, bone marrow, and skin fibroblasts were established from 8 different patients with rheumatoid arthritis who were undergoing knee or hip surgery. Resting or activated fibroblasts were cocultured with either CD4 T cells or neutrophils, and the degree of leukocyte survival, apoptosis, and proliferation were measured.

Results

Fibroblasts derived from all 3 sites supported increased survival of CD4 T cells, mediated principally by interferon‐β. However, synovial and bone marrow fibroblasts shared an enhanced site‐specific ability to maintain CD4 T cell survival in the absence of proliferation, an effect that was independent of fibroblast activation or proliferation but required direct T cell–fibroblast cell contact. In contrast, fibroblast‐mediated neutrophil survival was less efficient, being independent of the site of origin of the fibroblast but dependent on prior fibroblast activation, and mediated solely by soluble factors, principally granulocyte–macrophage colony‐stimulating factor.

Conclusion

These results suggest an important functional role for fibroblasts in the differential accumulation of leukocyte subsets in a variety of tissue microenvironments. The findings also provide a potential explanation for site‐specific differences in the pattern of T cell and neutrophil accumulation observed in chronic inflammatory diseases.
Regulation of pre–B cell colony‐enhancing factor by STAT‐3–dependent interleukin‐6 trans‐signaling: Implications in the pathogenesis of rheumatoid arthritis
Authors: Nowell Mari A. , Richards Peter J. , Fielding Ceri A. , Ognjanovic Simona , Topley Nick , Williams Anwen S. , Bryant‐Greenwood Gillian , Jones Simon A.
Published: June 2006

Objective

To determine whether interleukin‐6 (IL‐6) trans‐signaling directs the expression of pre–B cell colony‐enhancing factor (PBEF) in vitro and in vivo.

Methods

Complementary DNA from rheumatoid arthritis (RA) synovial fibroblasts treated with IL‐6 and soluble IL‐6 receptor (sIL‐6R) was used to probe a cytokine microarray. PBEF regulation by the IL‐6–related cytokines, IL‐6, sIL‐6R, oncostatin M (OSM), IL‐11, and leukemia inhibitory factor (LIF) was determined by reverse transcription–polymerase chain reaction analysis. IL‐6–mediated STAT‐3 regulation of PBEF was determined using a cell‐permeable STAT‐3 inhibitor peptide. Antigen‐induced arthritis (AIA) was induced in wild‐type (IL‐6+/+) and IL‐6–deficient (IL‐6−/−) mice. PBEF and STAT were detected by immunohistochemistry, immunoblotting, and electrophoretic mobility shift assay. Synovial levels of PBEF were quantified by enzyme immunoassay.

Results

IL‐6 trans‐signaling regulated PBEF in a STAT‐3–dependent manner. In addition, PBEF was regulated by the IL‐6–related cytokine OSM, but not IL‐11 or LIF. Flow cytometric analysis of the IL‐6–related cognate receptors suggested that OSM regulates PBEF via its OSM receptor β and not its LIF receptor. The involvement of PBEF in arthritis progression was confirmed in vivo, where induction of AIA resulted in a 4‐fold increase in the synovial expression of PBEF. In contrast, little or no change was observed in IL‐6−/− mice, in which the inflammatory infiltrate was markedly reduced and synovial STAT‐1/3 activity was also impaired. Analysis of human RA synovial tissue confirmed that PBEF immunolocalized in apical synovial membrane cells, endothelial cells, adipocytes, and lymphoid aggregates. Synovial fluid levels of PBEF were significantly higher in RA patients than in osteoarthritis patients.

Conclusion

Experiments presented herein demonstrate that PBEF is regulated via IL‐6 trans‐signaling and the IL‐6–related cytokine OSM. PBEF is also actively expressed during arthritis. Although these data confirm an involvement of PBEF in disease progression, the consequence of its action remains to be determined.
The catabolic pathway mediated by Toll‐like receptors in human osteoarthritic chondrocytes
Authors: Kim Hyun Ah , Cho Mi‐La , Choi Hye Young , Yoon Chang Sik , Jhun Joo Yeon , Oh Hey Jwa , Kim Ho‐Youn
Published: June 2006

Objective

To examine the catabolic pathways mediated by Toll‐like receptor (TLR) ligands in human osteoarthritic (OA) chondrocytes.

Methods

The presence of TLRs in OA and non‐OA articular cartilage was analyzed by immunohistochemistry. The regulation of TLR messenger RNA (mRNA) by interleukin‐1 (IL‐1) and tumor necrosis factor α (TNFα) was analyzed by reverse transcription–polymerase chain reaction. For stimulation of TLR‐2 and TLR‐4, chondrocytes were treated with Staphylococcus aureus peptidoglycan and lipopolysaccharides (LPS), respectively. Production of matrix metalloproteinases (MMPs) 1, 3, and 13 and prostaglandin E2 (PGE2) was evaluated by enzyme‐linked immunosorbent assay. Production of nitric oxide (NO) was analyzed by the Griess reaction. Regulation of cyclooxygenase 2 protein and phosphorylation of MAPKs (p38, ERK, and JNK) were evaluated by Western blotting or solid‐phase kinase assay. NF‐κB activation was evaluated by electrophoretic mobility shift assay.

Results

Expression of TLRs 2 and 4 was up‐regulated in lesional areas of OA cartilage. Treatment with IL‐1, TNFα, peptidoglycan, and LPS all significantly up‐regulated TLR‐2 mRNA expression in cultured chondrocytes. Production of MMPs 1, 3, and 13 and of NO and PGE2 was significantly increased after treating chondrocytes with either of the TLR ligands. Prolonged culture of cartilage explants with TLR ligands also led to a significant increase in the release of proteoglycan and type II collagen degradation product. Treatment with TLR ligands led to phosphorylation of all 3 MAPKs and activation of NF‐κB.

Conclusion

We found that TLRs are increased in OA cartilage lesions. TLR‐2 and TLR‐4 ligands strongly induce catabolic responses in chondrocytes. Modulation of TLR‐mediated signaling as a therapeutic strategy would require detailed elucidation of the signaling pathways involved.
Identification of genes modulated in rheumatoid arthritis using complementary DNA microarray analysis of lymphoblastoid B cell lines from disease‐discordant monozygotic twins
Authors: Haas Christian S. , Creighton Chad J. , Pi Xiujun , Maine Ira , Koch Alisa E. , Haines G. Kenneth , Ling Song , Chinnaiyan Arul M. , Holoshitz Joseph
Published: June 2006

Objective

To identify disease‐specific gene expression profiles in patients with rheumatoid arthritis (RA), using complementary DNA (cDNA) microarray analyses on lymphoblastoid B cell lines (LCLs) derived from RA‐discordant monozygotic (MZ) twins.

Methods

The cDNA was prepared from LCLs derived from the peripheral blood of 11 pairs of RA‐discordant MZ twins. The RA twin cDNA was labeled with cy5 fluorescent dye, and the cDNA of the healthy co‐twin was labeled with cy3. To determine relative expression profiles, cDNA from each twin pair was combined and hybridized on 20,000‐element microarray chips. Immunohistochemistry and real‐time polymerase chain reaction were used to detect the expression of selected gene products in synovial tissue from patients with RA compared with patients with osteoarthritis and normal healthy controls.

Results

In RA twin LCLs compared with healthy co‐twin LCLs, 1,163 transcripts were significantly differentially expressed. Of these, 747 were overexpressed and 416 were underexpressed. Gene ontology analysis revealed many genes known to play a role in apoptosis, angiogenesis, proteolysis, and signaling. The 3 most significantly overexpressed genes were laeverin (a novel enzyme with sequence homology to CD13), 11β‐hydroxysteroid dehydrogenase type 2 (a steroid pathway enzyme), and cysteine‐rich, angiogenic inducer 61 (a known angiogenic factor). The products of these genes, heretofore uncharacterized in RA, were all abundantly expressed in RA synovial tissues.

Conclusion

Microarray cDNA analysis of peripheral blood–derived LCLs from well‐controlled patient populations is a useful tool to detect RA‐relevant genes and could help in identifying novel therapeutic targets.
N‐methylation of Nα‐acylated, fully Cα‐methylated, linear, folded peptides: Synthetic and conformational aspects
Authors: Moretto Alessandro , Crisma Marco , Kaptein Bernard , Broxterman Quirinus B. , Toniolo Claudio
Published: June 2006

Peptides characterized by single or multiple N‐methylated, Cα‐trisubstituted (e.g., protein) amino acids are of great interest in medicinal chemistry. Several naturally occurring peptides, remarkably stable to enzymatic attacks, are based on N‐methylated residues. The classical conditions (CH3I/Ag2O in DMF, 24 h, room temperature) for N‐methylation of the peptide function are useful tools for distinguishing solvent exposed from intramolecularly H‐bonded –CO–NH– groups in peptides. In this work we have extended this reaction to Nα‐acylated, linear peptides based exclusively on helicogenic Cα‐tetrasubstituted α‐amino acids, e.g., Aib (α‐aminoisobutyric acid) or (αMe)Nva (Cα‐methyl norvaline) residues. Under the experimental conditions used, only amide monomethylation (on the N‐terminal, acylated, residue) takes place. Methylation of internal peptide groups linking two Cα‐tetrasubstituted residues was not observed. Our FT–IR absorption, NMR, and X‐ray diffraction investigations support the view that the β‐turn and 310‐helical conformations preferred by the original peptides are not dramatically perturbed in the derivatives monomethylated at position 1. In particular, the tertiary amide bonds are trans. Conversely, the packing modes in the crystals are strongly influenced by the reduction of the number of H‐bonding donors. The MeXxx–Xxx peptide bond is readily disrupted under mild acidic conditions. © 2006 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 84: 553–565, 2006

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Calcite Mesocrystals: “Morphing” Crystals by a Polyelectrolyte
Authors: Wang Tongxin , Antonietti Markus , Cölfen Helmut
Published: June 2006

Crystallization of calcite from different concentrated calcium chloride solutions by the CO2vapor diffusion technique in the presence of polystyrenesulfonate (PSS) yields defined assemblies of nanoparticles with unusual morphology. From the typical calcite rhombohedra, the morphology can be systematically varied via rounded edges and truncated triangles to concavely bent lens‐like shapes. Although these “crystals” are apparently well facetted as observed in light microscopy, electron microscopy analysis and BET isotherms reveal that the structures are highly porous and are composed of almost perfectly three‐dimensionally aligned calcite nanocrystals, scaffolded to the final, partly curved structures. The formation of all mesostructures is discussed within the framework of a polymer‐mediated structure‐formation process, in which the polymer is acting in four different ways. The present model case also provides evidence for the importance of nonclassical mesoscopic processes in polymer‐controlled crystallization in general.
Covalent Connection of Individualized, Neutral, Dendronized Polymers on a Solid Substrate Using a Scanning Force Microscope
Authors: Al‐Hellani Rabie , Barner Jörg , Rabe Jürgen P. , Schlüter A. Dieter
Published: June 2006

The synthesis of a neutral, high‐molar‐mass, acrylamide‐based, third‐generation dendronized polymer (denpol) with a defined number of azide groups at its periphery is reported. An attach‐to route is used in which a first‐generation denpol is reacted with second‐generation (G2) dendrons. The degree of structure perfection of the resulting denpol is quantified as 99.8 %. This value was obtained after the introduction of a fluorescence label at the sites that remained unaffected by the dendronization. The high coverage was independently confirmed for the dendronization of another first‐generation polymer and a closely related G2 dendron. The third‐generation denpol resulting from the first dendronization experiment was spin‐coated as a sub‐monolayer onto highly oriented graphite precoated with an ultrathin layer of C12H25NH2, which was introduced to provide a well‐defined substrate for denpol adsorption and manipulation. Scanning force microscopy revealed single denpols, which could be moved across the surface and “welded” by covalent cross‐linking induced by photochemical decomposition of the azides into highly reactive nitrenes. The successful formation of covalent bonds between two denpols was confirmed by mechanically challenging the link with the scanning force microscope (SFM) tip. This is the second reported case of a move–connect–prove sequence using polymers and the SFM, which for the first time employs noncharged denpols, thus widening the applicability of this method significantly.
Highly Efficient Synthesis of Enantiopure Diacetylated C2‐Symmetric Diols by Ruthenium‐ and Enzyme‐Catalyzed Dynamic Kinetic Asymmetric Transformation (DYKAT)
Authors: Martín‐Matute Belén , Edin Michaela , Bäckvall Jan‐E.
Published: June 2006

Highly efficient synthesis of enantiopure diacetates of 2,4‐pentanediol and 2,5‐hexanediol starting from commercially available mixtures of the diols (dl/meso ≈1:1) has been realized by combining a fast ruthenium‐catalyzed epimerization with an enzymatic transesterification. The in situ coupling of these two processes produces the diacetates in high yield in >99 % enantiomeric excess.
Fluorogenic 1,3‐Dipolar Cycloaddition within the Hydrophobic Core of a Shell Cross‐Linked Nanoparticle
Authors: O'Reilly Rachel K. , Joralemon Maisie J. , Hawker Craig J. , Wooley Karen L.
Published: June 2006

Using either nitroxide mediated polymerization (NMP) or reversible addition fragmentation transfer (RAFT) techniques, novel block copolymers that present terminal acetylenes, in the side chain of the styrenic block, were obtained with narrow polydispersities and targeted molecular weights. For the conversion of these acetylene‐functionalized polymers to amphiphilic block copolymers, RAFT techniques were preferred. Mild protection/deprotection chemistries were employed which were compatible with the incorporation of the acetylene functionality in the hydrophobic segment. These acetylene‐functionalized, Click‐readied amphiphilic block copolymers were then self‐assembled and cross‐linked to afford shell cross‐linked knedel‐like (SCK) nanoparticles that contained acetylene groups in the core domain. The hydrodynamic diameters (Dh) of the block copolymer micelles and nanoparticles were determined by dynamic light scattering (DLS), and the dimensions of the nanoparticles were characterized using tapping‐mode atomic force microscopy (AFM) and transmission electron microscopy (TEM). The chemical availability of the Click functionality within the core domain of the SCKs was investigated using the copper(I)‐catalyzed 1,3‐dipolar fluorogenic cycloaddition with a non‐fluorescent 3‐azidocoumarin profluorophore to afford intensely fluorescent nanoparticles.
Conjecture: Imines as Unidirectional Photodriven Molecular Motors—Motional and Constitutional Dynamic Devices
Authors: Lehn Jean‐Marie
Published: June 2006

Compounds containing the CN group, such as imines and their derivatives, may undergo syn–anti isomerization by two different routes: 1) photochemically, by out‐of‐plane rotation around the carbon‐nitrogen double bond through a “perpendicular” form, and 2) thermally, by in‐plane nitrogen inversion through a “linear” transition state. When the two interconversions occur in sequence, a full, closed process is accomplished, restoring the initial state of the system along two different steps. In a chiral imine‐type compound, for example, with an asymmetric center next to the CN function, photoinduced rotation may be expected to occur in one sense in preference to the opposite one. Thus, photoisomerization followed by thermal isomerization in a chiral imine compound generates unidirectional molecular motion. Generally, imine‐type compounds represent unidirectional molecular photomotors converting light energy into mechanical motion. As they are also able to undergo exchange of the carbonyl and amine partners, they present constitutional dynamics. Thus, imine‐type compounds are double dynamic, motional, and constitutional devices.
Patient treatment preferences in localized prostate carcinoma: The influence of emotion, misconception, and anecdote
Authors: Denberg Thomas D. , Melhado Trisha V. , Steiner John F.
Published: June 2006

BACKGROUND.

Multiple therapeutic options exist for localized prostate carcinoma, without conclusive evidence to guide the choice of treatment. Thus, treatment should reflect trade‐offs between the probability of curing disease and the desire to avoid treatment‐associated side effects. Factors that actually influence patient treatment preferences are poorly understood.

METHODS.

We reviewed medical records and carried out in‐depth, semistructured interviews of 20 men with newly‐diagnosed, clinically‐localized prostate carcinoma in a Veterans Affairs Hospital following their first consultations with urologists and before treatments were initiated. Six to eight months after treatment, we carried out follow‐up interviews. Interviews explored beliefs and attitudes about prostate cancer and treatment options, emotional reactions to the diagnosis, treatment preferences, information sources, and perceptions of interactions with urologists.

RESULTS.

Patient treatment preferences were not based on careful assessments of numerical risks for various clinical outcomes. Instead, feelings of fear and uncertainty contributed to a desire for rapid treatment, and specific preferences were profoundly influenced by misconceptions, especially about prostatectomy, and by anecdotes about the experiences of others with cancer. Few patients wanted to seek second opinions. Most patients received treatments that matched their initial preferences. Afterwards, they justified their choices in terms of the same misconceptions and anecdotal influences invoked during treatment deliberation.

CONCLUSIONS.

For men with localized prostate carcinoma, the treatment decision‐making process would benefit from interventions that moderate feelings of fear and a desire for rapid treatment, dispel common and powerful misconceptions about prostate cancer and its therapies, and help patients avoid over‐reliance on anecdotes. Cancer 2006. © 2006 American Cancer Society.
Overexpression of podoplanin in oral cancer and its association with poor clinical outcome
Authors: Yuan Ping , Temam Stephane , El‐Naggar Adel , Zhou Xian , Liu Diane D. , Lee J. Jack , Mao Li
Published: June 2006

BACKGROUND.

Podoplanin is a mucin‐like glycoprotein that is important in lymphangiogenesis but not blood vessel formation. Recent studies suggested a potential role of podoplanin in certain tumor cells. The purpose of the current study was to determine the role of podoplanin in head and neck squamous cell carcinoma (HNSCC).

METHODS.

Podoplanin expression was analyzed in 35 patients with HNSCC including 16 oral tumors and 19 hypopharyngeal tumors by immunohistochemical analysis and the association between the podoplanin expression status and patients' clinical and pathologic characteristics was evaluated. An independent set of 60 patients with oral tongue cancer was then analyzed for associations between the podoplanin expression status and patients' clinical and pathologic characteristics, including survivals.

RESULTS.

Podoplanin was not expressed in normal oral epithelial cells but was detected in some hyperplastic and dysplastic lesions. High podoplanin expression was found in 20 (57%) of the 35 tumors and was more frequent in tumors with lymph node metastasis, particularly for tumors in the oral cavity. In the second set of 60 oral tongue cancers, 36 (60%) expressed high levels of podoplanin. Patients whose tumors expressed high levels of podoplanin had a statistically significantly higher rate of lymph node metastasis (P < .0001). Patients with lymph node metastasis and high‐level podoplanin showed the shortest disease‐specific survival (P = .0004) than other patients.

CONCLUSIONS.

Podoplanin is involved in oral tumorigenesis and may serve as a predictor for lymph node metastasis and poor clinical outcome. Cancer 2006. © 2006 American Cancer Society.
Patterning of coronary arteries in wildtype and connexin43 knockout mice
Authors: Clauss Sarah B. , Walker Diana L. , Kirby Margaret L. , Schimel Dan , Lo Cecilia W.
Published: June 2006

Abnormal patterning of coronary arteries (CAs) is a clinically significant problem, and as yet, few animal models have been systematically investigated for coronary patterning defects. Here we characterized coronary artery (CA) insertion and branching patterns of the proximal coronary stems in the hearts of wildtype and heterozygous connexin43 knockout (Cx43α1 KO) mice. This study entailed the use of high‐resolution micro CT imaging for three‐dimensional coronary reconstructions. MicroCT of 17 wildtype mice showed a remarkably consistent pattern of CA deployment in the normal mouse heart. Two main CA stems are inserted from the left and right into the aorta. The right coronary artery then branches immediately into the right main and the septal‐conal branch, while the left coronary artery branches further distally into the circumflex and the anterior descending CA. This patterning of CA anatomy was confirmed by histology, and by using a vascular smooth muscle or endothelial cell specific lacZ reporter gene to delineate the CAs. A parallel analysis of 25 heterozygous Cx43α1 KO mouse hearts showed 22 had defects in patterning of the CAs. They exhibited a wide variation in CA anatomy, including abnormal origin and course of the main CA stems, multiple accessories, and dual septal‐conal branches. Overall, these studies show loss of one Cx43α1 allele (haploinsufficiency) leads to a high incidence of coronary patterning defects. These findings suggest CA patterning is sensitive to Cx43α1 gene dosage. Developmental Dynamics 235:2786–2794, 2006. Published 2006 Wiley‐Liss, Inc.
Cover Picture: Rigid Bisphenanthrolines: Synthesis, Structure and Self‐Assembly at a Solid–Liquid Interface (Eur. J. Org. Chem. 14/2006)
Authors: Schmittel Michael , Kalsani Venkateshwarlu , Jäckel Frank , Rabe Jüurgen P. , Bats Jan W. , Fenske Dieter
Published: June 2006

The cover picture shows a comparison between 2D and 3D architectures of bisphenanthrolines. The architecture of 2D self‐assembled surface monolayers was explored by scanning tunneling microscopy (STM) at the solid–liquid interface, while 3D structures of the same compounds were elucidated in the solid state by X‐ray structure analysis. Details are discussed in the article by M. Schmittel et al. on p. 3079 ff.
Interindividual variability of canalicular ATP-binding-cassette (ABC)–transporter expression in human liver
Authors: Meier Yvonne , Pauli-Magnus Christiane , Zanger Ulrich M. , Klein Kathrin , Schaeffeler Elke , Nussler Andreas K. , Nussler Natascha , Eichelbaum Michel , Meier Peter J. , Stieger Bruno
Published: June 2006

Interindividual variability in hepatic canalicular transporter expression might predispose to the development of hepatic disorders such as acquired forms of intrahepatic cholestasis. We therefore investigated expression patterns of bile salt export pump (BSEP,

ABCB11

), multidrug resistance protein 3 (MDR3,

ABCB4

), multidrug resistance associated protein 2 (MRP2,

ABCC2

) and multidrug resistance protein 1 (MDR1, ABCB1) in healthy liver tissue of a white population. Protein expression levels were correlated with specific single nucleotide polymorphisms (SNPs) in the corresponding transporter genes. Hepatic protein expression levels from 110 individuals undergoing liver resection were assessed by Western blot analysis of liver plasma membranes enriched in canalicular marker enzymes. Each individual was genotyped for the following synonymous (s) and nonsynonymous (ns) SNPs:

ABCB11:

(ns:1457T>C and 2155A>G),

ABCB4:

(ns:3826A>G) and

ABCC2

(ns:1286G>A,3600T>A and 4581G>A) and

ABCB1

(ns:2677G>T/A and s:3435C>T). Transporter expression followed unimodal distribution. However, of all tested individuals 30% exhibited a

high expression

and 32% a

low or very low expression

phenotype for at least one of the four investigated transport proteins. Transporter expression levels did not correlate with age, sex, underlying liver disease, or presurgery medication. However,

low

BSEP expression was associated with the 1457C-allele in

ABCB11

(

P =

.167) and

high

MRP2 expression was significantly correlated with the 3600A and 4581A

ABCC2

variants (

P =

.006).

In conclusion

, the results demonstrate a considerable interindividual variability of canalicular transporter expression in normal liver. Furthermore, data suggest a polymorphic transporter expression pattern, which might constitute a risk factor for the development of acquired forms of cholestatic liver diseases.

Supplementary material for this article can be found on the HEPATOLOGY website
(http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html)
Constitutive androstane receptor (CAR) ligand, TCPOBOP, attenuates Fas-induced murine liver injury by altering Bcl-2 proteins
Authors: Baskin-Bey Edwina S. , Huang Wendong , Ishimura Norihisa , Isomoto Hajime , Bronk Steven F. , Braley Karen , Craig Ruth W. , Moore David D. , Gores Gregory J.
Published: June 2006

The constitutive androstane receptor (CAR) modulates xeno- and endobiotic hepatotoxicity by regulating detoxification pathways. Whether activation of CAR may also protect against liver injury by directly blocking apoptosis is unknown. To address this question, CAR wild-type (CAR+/+) and CAR knockout (CAR−/−) mice were treated with the CAR agonist 1,4-bis[2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP) and then with the Fas agonist Jo2 or with concanavalin A (ConA). Following the administration of Jo2, hepatocyte apoptosis, liver injury, and animal fatalities were abated in TCPOBOP-treated CAR+/+ but not in CAR−/− mice. Likewise, acute and chronic ConA-mediated liver injury and fibrosis were also reduced in wild-type versus CAR−/− TCPOBOP-treated mice. The proapoptotic proteins Bak (Bcl-2 antagonistic killer) and Bax (Bcl-2-associated X protein) were depleted in livers from TCPOBOP-treated CAR+/+ mice. In contrast, mRNA expression of the antiapoptotic effector myeloid cell leukemia factor-1 (

Mcl-1

) was increased fourfold.

Mcl-1

promoter activity was increased by transfection with CAR and administration of TCPOBOP in hepatoma cells, consistent with a direct CAR effect on

Mcl-1

transcription. Indeed, site-directed mutagenesis of a putative CAR consensus binding sequence on the

Mcl-1

promoter decreased

Mcl-1

promoter activity.

Mcl-1

transgenic animals demonstrated little to no acute liver injury after administration of Jo2, signifying

Mcl-1

cytoprotection.

In conclusion

, these observations support a prominent role for CAR cytoprotection against Fas-mediated hepatocyte injury via a mechanism involving upregulation of Mcl-1 and, likely, downregulation of Bax and Bak.
Photo‐Fries Rearrangement of Carbazol‐2‐yl Sulfonates: Efficient Tool for the Introduction of Sulfonyl Groups into Polycyclic Aromatic Compounds
Authors: Crevatín Laura K. , Bonesi Sergio M. , Erra‐Balsells Rosa
Published: June 2006

Systematic studies on the photo‐Fries rearrangement of different 9H‐carbazol‐2‐yl sulfonates 2 have shown that this type of conversion can be readily used for the preparative‐scale introduction of alkyl‐ or arylsulfonyl groups into polycyclic aromatic compounds under very mild conditions. A series of new 1‐sulfonyl‐ (3) or 3‐sulfonyl‐9H‐carbazoles (4) were prepared in medium‐to‐good yields, and characterized by UV/VIS, 1H‐NMR, and 13C‐NMR spectroscopy, as well as by elemental analysis. Effects of irradiation wavelength, solvent polarity, presence or absence of O2, and photosensitizers were studied in detail.
Development of the tumor vascular bed in response to hypoxia‐induced VEGF‐A differs from that in tumors with constitutive VEGF‐A expression
Authors: Roodink Ilse , van der Laak Jeroen , Kusters Benno , Wesseling Pieter , Verrijp Kiek , de Waal Robert , Leenders William
Published: June 2006

Tumors arise initially as avascular masses in which central hypoxia induces expression of vascular endothelial growth factor‐A (VEGF‐A) and subsequently tumor vascularization. However, VEGF‐A can also be constitutively expressed as a result of genetic events. VEGF‐A is alternatively spliced to yield at least 6 different isoforms. Of these, VEGF‐A121 is freely diffusible whereas basically charged domains in the larger isoforms confer affinity for cell surface or extracellular matrix components. We previously reported that in a mouse brain metastasis model of human melanoma, VEGF‐A121 induced a qualitatively different tumor vascular phenotype than VEGF‐A165 and VEGF‐A189: in contrast to the latter ones, and VEGF‐A121 did not induce a neovascular bed but rather led to leakage and dilatation of preexistent brain vessels. Here, we correlate vascular phenotypes with spatial VEGF‐A expression profiles in clinical brain tumors (low grade gliomas; n = 6, melanoma metastases; n = 4, adenocarcinoma metastases; n = 4, glioblastoma multiforme; n = 3, sarcoma metastasis; n = 1, renal cell carcinoma metastasis; n = 1). We show that tumors that constitutively express VEGF‐A present with different vascular beds than tumors in which VEGF‐A is expressed as a response to central hypoxia. This phenotypic difference is consistent with a model where in tumors with constitutive VEGF‐A expression, all isoforms exert their effects on vasculature, resulting in a classical angiogenic phenotype. In tumors where only central parts express hypoxia‐induced VEGF‐A, the larger angiogenic isoforms are retained by extracellular matrix, leaving only freely diffusible VEGF‐A121 to exert its dilatation effects on distant vessels. © 2006 Wiley‐Liss, Inc.
PTEN, Akt, and GSK3β signalling in rat primary cortical neuronal cultures following tumor necrosis factor‐α and trans‐4‐hydroxy‐2‐nonenal treatments
Authors: Rickle A. , Behbahani H. , Ankarcrona M. , Winblad B. , Cowburn R.F.
Published: June 2006

PTEN is a dual phosphatase that negatively regulates the phosphatidylinositol 3‐kinase (PI3K)/Akt signalling pathway important for cell survival. We determined effects of the inflammation and oxidative stresses of tumor necrosis factor‐α (TNFα) and trans‐4‐hydroxy‐2‐nonenal (HNE), respectively, on PTEN, Akt, and GSK3β signalling in rat primary cortical neurons. The inhibitors bisperoxovanadium [bpV(Pic)] and LY294002 were also used to determine PTEN and PI3K involvement in TNFα and HNE modulation of neuronal cell death. PTEN inhibition with bpV(Pic) alone did not affect Ser473Akt or Ser9GSK3β phosphorylation. Instead, effects of this inhibitor were manifest when it was used together with TNFα and to a lesser extent with HNE. TNFα together with PTEN inhibition increased phosphorylation of Ser473Akt and Ser9GSK3β. TNFα and HNE both gave decreased numbers of viable and increased numbers of early apoptotic neurons. PTEN inhibition partially reversed the toxic effect of TNFα as shown by an increased number of viable and a decreased number of early apoptotic neurons. All effects were reversed by PI3K inhibition. HNE together with inhibition of PTEN gave increased Ser473Akt but not Ser9GSK3β phosphorylation and no effects on the number of viable or early apoptotic cells. In conclusion, PTEN inhibition gives a mild reversal of TNFα‐ but not HNE‐induced cell death via the PI3K pathway. © 2006 Wiley‐Liss, Inc.
Effect of the proteinaceous wheat xylanase inhibitor XIP‐I on the performances of an Aspergillus niger xylanase in breadmaking
Authors: Rouau Xavier , Daviet Stéphanie , Tahir Tariq , Cherel Benjamin , Saulnier Luc
Published: June 2006

The functionality of the proteinaceous wheat xylanase inhibitor XIP‐I in Aspergillus niger endoxylanase‐aided breadmaking was investigated using small‐scale breadmaking and in vitro experiments. At an optimal dosage for an increase in bread volume, the endoxylanase provoked a ∼15% increase of loaf volume in standard flour experiments, but the dough was significantly more sticky than in the control. No variations in bread volumes were observed in the presence of added XIP‐I in endoxylanase dough but stickiness was much reduced. Arabinoxylan (AX) solubilisation from flour cell wall material was practically unaffected with XIP‐I, and the viscosity of dough water extracts and AX intrinsic viscosity were slightly enhanced. In other breadmaking experiments using a flour from which water extractable material was inactivated, or a reconstituted flour (starch, gluten, water extractable arabinoxylans (WEAXs), water unextractable arabinoxylans (WUAXs)), no differences in loaf volumes were observed between control, endoxylanase and endoxylanase/XIP‐I breads, but the high stickiness induced by endoxylanase was totally corrected by XIP‐I. In these doughs, AX solubilisation was slightly affected by XIP‐I whereas water extract viscosity and WEAX intrinsic viscosity were much higher than in endoxylanase doughs. In vitro experiments with purified AX and A. niger endoxylanase and XIP‐I confirmed these findings, showing that the endoxylanase inhibition by XIP‐I had more effect on the characteristics measured on WEAX (specific and intrinsic viscosities) than those measured on WUAX (AX solubilisation). Premixing substrate, endoxylanase and inhibitor in different combinations showed that XIP‐I had a tendancy to bind WUAX, but not WEAX, which changed the balance between enzymic AX solubilisation and AX depolymerisation. As a result, a high viscosity of water extracts was preserved, which is beneficial for dough handling properties. Copyright © 2006 Society of Chemical Industry
Accordion BIRD‐HMBC experiments: improved one‐bond correlation suppression in accordion heteronuclear multiple‐bond correlation‐type experiments
Authors: Furrer Julien
Published: June 2006

Modifications of the BIRD‐HMBC experiment, in which the accordion principle and a constant time period have been introduced, are presented. With the simple accordion BIRD‐HMBC, the use of a BIRDr, X element in the middle of the variable long‐range couplings evolution period efficiently eliminates unwanted 1JCH signals and samples a broad range of long‐range heteronuclear couplings. While the accordion BIRD‐HMBC experiment shows reduced F1 modulation, superior suppression of unwanted 1JCH signals and sensitivity comparable to the ACCORD‐HMBC, the addition of another constant time period suppresses F1 modulation due to 1H‐1H coupling, while preserving the excellent suppression of unwanted 1JCH signals. The constant‐time (CT) accordion BIRD‐HMBC experiment combines sensitivity similar to the CIGAR‐HMBC and superior suppression of unwanted 1JCH signals. Results of identically optimized ACCORD‐HMBC, accordion BIRD‐HMBC, CT accordion BIRD‐HMBC and CIGAR‐HMBC experiments performed on a sample of strychnine are compared and discussed. Copyright © 2006 John Wiley & Sons, Ltd.
Capillary Pressure Curves of Sphere Packings: Correlation of Experimental Results and Comparison with Predictions from a Network Model of Pore Space
Authors: Dodds John A. , Srivastava Prashant
Published: June 2006

A water suction apparatus has been used to measure capillary pressure curves of glass beads in both loose and dense random packings. Four different mono‐sized samples and four ternary mixtures have been examined. It is shown that the experimental results can be reduced to a single curve by means of a correlation based on the specific surface and porosity. This correlation is further validated by experiments with a series of five grades of diatomaceous filter aid. The experimental desaturation process is simulated with a 2D network model of pore space, involving packing based on pore size distributions calculated from the tetrahedral packing model. This gives capillary pressure curves comparable with the experimental results for sphere packing, which correlate with the experimental results. Therefore, the method provides a relationship between grain space and pore space through capillary pressure curves.
Application of Mercury Intrusion Porosimetry for Characterization of Combined Micro‐ and Mesoporous Zeolites
Authors: Groen Johan C. , Brouwer Sander , Peffer Louk A. A. , Pérez‐Ramírez Javier
Published: June 2006

Combined micro‐ and mesoporous ZSM‐5 zeolites with different mesopore sizes have been comparatively investigated using mercury‐intrusion porosimetry (MIP) and N2 gas adsorption. N2 adsorption and MIP complement each other and a fairly good correlation has been obtained for the mesopore sizes and volumes derived from both techniques, confirming an adequate accessibility of the newly created mesoporosity. Elastic compression of the mesoporous zeolites during the mercury‐intrusion experiments can account for the somewhat smaller average mesopore size and mesopore volume as derived from this technique. An excellent reproducibility of multiple mercury‐intrusion cycles proves the mechanical stability of the hierarchical porous zeolites. Besides, MIP provides supplementary information on the presence of macropores.