bluuebunny/crossref_metadata_2025 huggingface dataset:
The CGGGG insertion/deletion polymorphism of the IRF5 promoter is a strong risk factor for primary Sjögren's syndrome
Authors: Miceli‐Richard Corinne , Gestermann Nicolas , Ittah Marc , Comets Emmanuelle , Loiseau Pascale , Puechal Xavier , Hachulla Eric , Gottenberg Jacques‐Eric , Lebon Pierre , Becquemont Laurent , Mariette Xavier
Published: June 2009

Objective

Interferon regulatory factor 5 is a transcription factor involved in type I interferon (IFN) secretion. This study was undertaken to investigate whether a 5‐bp (CGGGG insertion/deletion) promoter polymorphism is involved in genetic predisposition to primary Sjögren's syndrome (SS) and to assess the functional consequences of this polymorphism.

Methods

The exploratory cohort consisted of 185 patients with primary SS and 157 healthy controls, and the replication cohort consisted of 200 patients with primary SS and 282 healthy controls. Levels of IRF5 messenger RNA (mRNA) were assessed at baseline and after in vitro infection with reovirus in peripheral blood mononuclear cells (PBMCs) from 30 patients with primary SS and from salivary gland epithelial cells that had been cultured for 4 weeks from patients with primary SS or sicca symptoms.

Results

Carriage of the IRF5 4R CGGGG allele was associated with a greatly increased risk of primary SS in both cohorts (odds ratio 2.00 [95% confidence interval 1.5–2.7], P = 6.6 × 10−6). The CGGGG insertion/deletion polymorphism alone was sufficient to explain the association of primary SS with IRF5. The level of IRF5 mRNA in PBMCs depended significantly on genotype (P = 0.002) and was correlated with the levels of mRNA for the IFN‐induced genes MX1 and IFITM1. Cultured salivary gland epithelial cells from patients carrying the 4R CGGGG IRF5 allele showed a high level of IRF5 mRNA (P = 0.04), which was amplified after reovirus infection (P = 0.026).

Conclusion

Our findings indicate an association of the CGGGG insertion/deletion polymorphism of the IRF5 promoter with primary SS. Patients carrying the 4R CGGGG IRF5 allele had a high level of mRNA for IRF5 in PBMCs and salivary gland epithelial cells, mainly after in vitro viral infection. Patients with high levels of mRNA for IRF5 also had high levels of mRNA for type I IFN–induced genes in PBMCs.
Functionalized Chiral Ionic Liquids: A New Type of Asymmetric Organocatalysts and Nonclassical Chiral Ligands
Authors: Luo Sanzhong , Zhang Long , Cheng Jin‐Pei
Published: June 2009

By judiciously anchoring functional groups onto chiral ionic liquids, functionalized chiral ionic liquids (FCILs) are emerging as a new type of asymmetric organocatalysts and nonclassical chiral ligands. This Focus Review highlights the applications of FCILs from the viewpoint of asymmetric catalysis. We focus mainly on the de novo designed and synthesized FCILs which likely still maintain the typical ionic liquids properties, and in a few cases relevant ionic liquid immobilized chiral catalysts are briefly discussed.
Isocyanate‐ and Isothiocyanate‐Derived RuIV‐Based Alkylidenes: Synthesis, Structure, and Activity
Authors: Kumar P. Santhosh , Wurst Klaus , Buchmeiser Michael R.
Published: June 2009

The synthesis and characterization of a series of isocyanate‐ and isothiocyanate‐derived second generation Grubbs–Hoveyda‐type ruthenium–alkylidene complexes, that is, [Ru(NCO)2(IMesH2)(CH‐2‐(2‐PrO)‐C6H4)] (1), [Ru(NCO)2(1,3‐dimesityl‐3,4,5,6‐tetrahydropyrimidin‐2‐ylidene)(=CH‐2‐(2‐PrO)‐C6H4)] (2), [Ru(NCS)2(IMesH2)(CH‐2‐(2‐PrO)‐C6H4)] (3), and [Ru(NCS)2(1,3‐dimesityl‐3,4,5,6‐tetrahydropyrimidin‐2‐ylidene)(CH‐2‐(2‐PrO)‐C6H4)] (4), and their activity in various metathesis reactions are described. Compounds 1–4 were prepared by reaction of the parent complexes [RuCl2(IMesH2)(CH‐2‐(2‐PrO)C6H4)] (5) (IMesH2=1,3‐bis‐(2,4,6‐trimethylphenyl)‐4,5‐dihydroimidazol‐2‐ylidene) and [RuCl2(1,3‐dimesityl‐3,4,5,6‐tetrahydropyrimidin‐2‐ylidene)(CH‐2‐(2‐PrO)‐C6H4)] (6) with silver cyanate and thiocyanate, respectively. The X‐ray structure of 1 was determined, confirming the isocyanate‐type bonding of the ligand. The isothiocyanate‐type bonding in 3 and 4 was unambiguously confirmed by IR and 13C NMR spectroscopy. The isocyanate‐derived complexes 1 and 2 were found to be excellent catalysts for the ring‐opening metathesis polymerization (ROMP) of cis‐cycloocta‐1,5‐diene (COD). Both 1 and 2 yielded poly(COD) with a trans‐content of about 80 %. First‐order kinetics with unprecedentedly high rate constants of polymerization (kp=0.068 and 0.26 s−1, respectively) were observed. Compounds 3 and 4 were also active initiators for the ROMP of COD, however, they generated poly(COD) with a cis‐content of 80 and 67 %, respectively. Complexes 1 and 2 also showed good catalytic activity in cross‐metathesis (CM) reactions. Finally, 1–4 were also found to be excellent catalysts for the regioselective cyclopolymerization of diethyl 2,2‐dipropargylmalonate (DEDPM), resulting in poly(DEDPM) almost entirely based on five‐membered repeat units, that is, cyclopent‐1‐ene‐1,2‐vinylenes.
Synthesis of Extremely π‐Extended Porphyrin Tapes from Hybrid meso‐meso Linked Porphyrin Arrays: An Approach Towards the Conjugation Length
Authors: Ikeda Toshiaki , Aratani Naoki , Osuka Atsuhiro
Published: June 2009

Directly meso‐meso, β‐β, β‐β triply linked porphyrin arrays are exceptional π‐conjugated molecules exhibiting remarkably red‐shifted absorption bands extending deeply in the IR region. In order to determine the effective conjugated length (ECL), we embarked on the synthesis of the porphyrin tapes far beyond the 12‐mer, which is the longest we have prepared so far. In this study, to find the compromise between the feasibility of the meso‐meso coupling reaction up to longer arrays and the sufficient solubility and chemical stability of the resultant porphyrin tapes, we prepared hybrid meso‐meso linked porphyrin arrays BOn up to 24‐mer, which have two different aryl groups, a 2,4,6‐tris(3,5‐di‐tert‐butylphenoxy) phenyl group (Ar1) and a 3,5‐dioctyloxy phenyl group (Ar2). All these arrays were effectively converted into the corresponding triply linked porphyrin tapes TBOn by oxidation with DDQ‐Sc(OTf)3. Importantly, the low energy Q‐band‐like absorption bands of TBOn are progressively red‐shifted with an increase in the number of porphyrins n until 16 but the red‐shift is saturated at n=16, indicating the ECL of the porphyrin tape to be around 14–16. The regularly introduced meso‐aryl bulky substituents impose facial encumbrance, hence leading to the effective suppression of π–π interactions as well as improvement of the chemical stabilities of TBOn.
Cover Picture: Reverse‐Selective Microporous Membrane for Gas Separation (Chem. Asian J. 7/2009)
Authors: Sawamura Ken‐ichi , Izumi Teruaki , Kawasaki Kiyotoshi , Daikohara Shintaro , Ohsuna Tetsu , Takada Mitsuko , Sekine Yasushi , Kikuchi Eiichi , Matsukata Masahiko
Published: June 2009

Reverse‐selective membranes, through which bigger molecules selectively permeate, are attractive for developing chemical processes utilizing hydrogen because they can maintain the high partial pressure of hydrogen required for further downstream utilization. Although several of these chemical processes are operated above 473 K, membranes with outstanding reverse‐selective separation performance at these temperatures are still to be reported. M. Matsukata et al. propose a new adsorption‐based reverse‐selective membrane that utilizes a Na cation occluded in a zeolitic framework. The membrane developed in this work enables selective permeation and separation of bigger polar molecules, such as methanol and water, from hydrogen above 473 K. For more information, see their Full Paper on page 1070 ff.

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The big carrot: High‐stakes incentives revisited
Authors: Brañas‐Garza Pablo , García‐Muñoz Teresa , Neuman Shoshana
Published: June 2009

Using an international dataset of about 35 000 subjects, this paper provides an empirical example of high‐stakes incentives in relation to religious practice. First, we show that incentives (based on absolute belief) play a salient role in religious performance. Second, we find that when both positive (heaven) and negative (hell) incentives are available the former are more effective than the latter. Specifically, it is shown that beliefs in heaven are much more relevant than beliefs in hell when estimating the production of religious commodities (church‐attendance and praying equations). Copyright © 2009 John Wiley & Sons, Ltd.
Modulation of Zn‐induced hyperinsulinemia/insulin resistance in Wistar rat fed modified poultry eggΨ
Authors: Taneja Satish Kumar , Mandal Reshu
Published: June 2009

Excessive bioavailability of Zn causes Cu and Mg deficiencies resulting in hyperglycemia and hyperinsulinemia/insulin resistance. These defects may ameliorate if the ionic imbalance in them is corrected. In view of this, three groups of rats were included in this study. Initially, they were fed on semi‐synthetic equicalories basal diet containing 20 mg Zn (control, group‐I), on 40 mg Zn (group‐II) and 80 mg Zn/kg diet (group‐III) respectively for 3 months. Thereafter, half of the rats in group‐II and III were shifted on Cu and Mg enriched modified poultry egg (MEΨ) mixed diets (groups‐IIME and IIIME) while the remaining were continued to feed on their respective diets for another 3 months completing a total of 6 months. Hyperglycemia, hyperinsulinemia, hypercortisolemia, hyperzincemia, hypercupremia and hypermagnesaemia with corresponding increase of lipid droplets in the zona fasciculate of adrenal cortex and reduction in liver glycogen content in rats of groups‐II and III were recorded. These changes were linked with a rise in Zn and fall in Cu and Mg in their liver. The addition of MEΨ in their diets led to fall of Zn and rise in liver Cu and Mg, and fall in serum Zn, Cu and Mg resulting in the improvement of glucose disposal, increase in insulin sensitivity, reduction in lipid droplets in zona fasciculate and increase in glycogen content in the liver approaching closer to the control group‐I. The data suggest that these MEΨ can serve as non‐pharmacological dietary supplement to prevent insulin resistance/hyperinsulinemia in populations who are at higher risk of diabetes mellitus either due to their genetic predisposition of excessive absorption and retention of Zn or due to higher Zn content in the food chain. © 2009 International Union of Biochemistry and Molecular Biology, Inc.
The ERK signaling cascade—Views from different subcellular compartments
Authors: Yao Zhong , Seger Rony
Published: June 2009

The extracellular signal‐regulated kinase cascade is a central signaling pathway that is stimulated by various extracellular stimuli. The signals of these stimuli are then transferred by the cascade's components to a large number of targets at distinct subcellular compartments, which in turn induce and regulate a large number of cellular processes. To achieve these functions, the cascade exhibits versatile and dynamic subcellular distribution that allows proper temporal and spatial modulation of the appropriate processes. In this review, we discuss the intracellular localizations of different components of the ERK cascade, and the impact of these localizations on their activation and specificity. © 2009 International Union of Biochemistry and Molecular Biology, Inc.
Good modeling practice for PAT applications: Propagation of input uncertainty and sensitivity analysis
Authors: Sin Gürkan , Gernaey Krist V. , Lantz Anna Eliasson
Published: June 2009

The uncertainty and sensitivity analysis are evaluated for their usefulness as part of the model‐building within Process Analytical Technology applications. A mechanistic model describing a batch cultivation of Streptomyces coelicolor for antibiotic production was used as case study. The input uncertainty resulting from assumptions of the model was propagated using the Monte Carlo procedure to estimate the output uncertainty. The results showed that significant uncertainty exists in the model outputs. Moreover the uncertainty in the biomass, glucose, ammonium and base‐consumption were found low compared to the large uncertainty observed in the antibiotic and off‐gas CO2 predictions. The output uncertainty was observed to be lower during the exponential growth phase, while higher in the stationary and death phases ‐ meaning the model describes some periods better than others. To understand which input parameters are responsible for the output uncertainty, three sensitivity methods (Standardized Regression Coefficients, Morris and differential analysis) were evaluated and compared. The results from these methods were mostly in agreement with each other and revealed that only few parameters (about 10) out of a total 56 were mainly responsible for the output uncertainty. Among these significant parameters, one finds parameters related to fermentation characteristics such as biomass metabolism, chemical equilibria and mass‐transfer. Overall the uncertainty and sensitivity analysis are found promising for helping to build reliable mechanistic models and to interpret the model outputs properly. These tools make part of good modeling practice, which can contribute to successful PAT applications for increased process understanding, operation and control purposes. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009
Theoretical analysis of excipient concentrations during the final ultrafiltration/diafiltration step of therapeutic antibody
Authors: Miao Fudu , Velayudhan Ajoy , DiBella Elsie , Shervin Jaclyn , Felo Michael , Teeters Mark , Alred Patricia
Published: June 2009

Diafiltration of a protein solution into a new buffer is a common final step in biopharmaceutical manufacturing. However, the excipient concentrations in the retentate are not always equal to their corresponding concentrations in the new buffer (diafiltration buffer). This phenomenon was observed repeatedly during diafiltration of different therapeutic monoclonal antibodies in which the concentrations of histidine and either sorbitol or sucrose (depending on which was chosen for the diafiltration buffer) in the retentate were lower than in the diafiltration buffer. Experimental studies and theoretical analyses of the ultrafiltration/diafiltration (UF/DF) step were carried out to determine the primary causes of the phenomenon and to develop a mathematical model capable of predicting retentate excipient concentrations. The analyses showed that retentate histidine concentration was low primarily because of repulsive charge interactions between positively‐charged histidine molecules and positively‐charged protein molecules, and that volume exclusion effects were secondary for like‐charged molecules. The positively‐charged protein molecules generate an electrical potential that cause an uneven distribution of charged histidine molecules. This interaction was used to construct a mathematical model based on the Poisson‐Boltzmann equation. The model successfully predicted the final histidine concentration in the diafiltered product (retentate) from the UF/DF development and production runs, with good agreement across a wide range of protein and histidine concentrations for four therapeutic monoclonal antibodies. The concentrations of uncharged excipients (sorbitol or sucrose) were also successfully predicted using previously established models, with volume exclusion identified as the primary cause of differences in uncharged excipient concentrations in the retentate and diafiltration buffer. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009
Biocompatible nanoparticles trigger rapid bacteria clustering
Authors: Larsen Mona Utne , Seward Matthew , Tripathi Anubhav , Shapley Nina C.
Published: June 2009

This study reveals an exciting phenomenon of stimulated bacteria clustering. Rapid aggregation and microbial arrest are shown to occur in Escherichia coli solutions of neutral pH when chitosan nanoparticles with positive zeta potential are added. Because chitosan nanoparticles can easily be dispersed in aqueous buffers, the rapid clustering phenomenon requires only minuscule nanoparticle concentrations and will be critical in developing new methods for extricating bacterial pathogens. This work establishes the dominant role of electrostatic attraction in bacteria‐nanoparticle interactions by varying the nanoparticle zeta potential from highly positive to strongly negative values, and by exploring concentration effects. For strongly negative nanoparticles, no clusters form, while aggregates are small and loose at intermediate conditions. In addition, optical density measurements indicate that over 90% of the suspended bacteria flocculate within seconds of being mixed with chitosan nanoparticles of a highly positive surface charge. Finally, the nanoparticles are significantly more efficient as a clustering agent compared to an equal mass of molecular chitosan in solution, as the bacteria‐nanoparticle clusters formed are substantially larger. The bacteria‐nanoparticle aggregation effect demonstrated here promises a rapid separation method for aiding pathogen detection and for flocculation of bacteria in fermentation processes. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009
Selection and growth regulation of genetically modified cells with hapten‐specific antibody/receptor tyrosine kinase chimera
Authors: Tanaka Kento , Kawahara Masahiro , Ueda Hiroshi , Nagamune Teruyuki
Published: June 2009

Although receptor tyrosine kinases (RTKs) play a pivotal role in the development and maintaining the homeostasis of the body, overexpression or mutation of RTKs often induces tumorigenesis or metastasis. To mimic the function of RTKs, we developed two fusion receptors consisting of anti‐fluorescein antibody single‐chain Fv, extracellular D2 domain of erythropoietin receptor and transmembrane/intracellular domains of epidermal growth factor receptor or c‐fms based on previously constructed antibody/cytokine receptor chimeras. The expression of these chimeric receptors in the hematopoietic cell line Ba/F3 and non‐hematopoietic cell line NIH/3T3 resulted in the activation of receptors themselves, downstream signaling molecules and cell proliferation in response to fluorescein‐conjugated BSA, leading to selective expansion of transduced cells up to almost 100%. These results indicate that the cognate antigen could activate the chimeric receptors even though the wild‐type extracellular domains were switched to the antibody fragment. This is the first study to show that our antigen‐mediated genetically modified cell amplification (AMEGA) system could be applied to non‐hematopoietic cells by utilizing antibody/RTK chimeras. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009
Perfluorocarbon facilitated O2 transport in a hepatic hollow fiber bioreactor
Authors: Chen Guo , Palmer Andre F.
Published: June 2009

A mathematical model describing O2 transport in a hepatic hollow fiber (HF) bioreactor supplemented with perfluorocarbons (PFCs) in the circulating cell culture media was developed to explore the potential of PFCs in properly oxygenating a bioartificial liver assist device (BLAD). The 2‐dimensional model is based on the geometry of a commercial HF bioreactor operated under steady‐state conditions. The O2 transport model considers fluid motion of a homogeneous mixture of cell culture media and PFCs, and mass transport of dissolved O2 in a single HF. Each HF consists of three distinct regions: (1) the lumen (conducts the homogeneous mixture of cell culture media and PFCs), (2) the membrane (physically separates the lumen from the extracapillary space (ECS), and (3) the ECS (hepatic cells reside in this compartment). In a single HF, dissolved O2 is predominantly transported in the lumen via convection in the axial direction and via diffusion in the radial direction through the membrane and ECS. The resulting transport equations are solved using the finite element method. The calculated O2 transfer flux showed that supplementation of the cell culture media with PFCs can significantly enhance O2 transport to the ECS of the HF when compared with a control with no PFC supplementation. Moreover, the O2 distribution and subsequent analysis of ECS zonation demonstrate that limited in vivo‐like O2 gradients can be recapitulated with proper selection of the operational settings of the HF bioreactor. Taken together, this model can also be used to optimize the operating conditions for future BLAD development that aim to fully recapitulate the liver's varied functions. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009
Cationic Porphyrins and Analogues as New DNA Topoisomerase I and II Inhibitors
Authors: Shuai Li , Wang Shaoru , Zhang Lixia , Fu Boqiao , Zhou Xiang
Published: June 2009

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A series of cationic porphyrins, and analogues such as cationic corroles and phthalocyanines were found to have biological activities towards topoisomerases I and II in vitro. Cationic porphyrins and phthalocyanines do not induce Topo I–DNA covalent complexes but inhibit topoisomerase I by direct binding to DNA, which limits topoisomerase I access to the DNA substrate. The lowest concentration where an inhibition effect is clearly visible of some derivatives is between 0.1 and 0.6 μM. Furthermore, some complexes were found to inhibit the activity of the topoisomerase II.
Susceptibility of Aedes aegypti and Culex quinquefasciatus Larvae to Gedunin‐Related Limonoids
Authors: Gurulingappa Hallur , Tare Vrushali , Pawar Pushpa , Tungikar Vijay , Jorapur Yogesh R. , Madhavi Sriram , Bhat Sujata V.
Published: June 2009

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The major non‐azadirachtin limonoids such as gedunin (1), epoxyazadiradione (3), nimbocinol (4), and nimolicinol (5) from Azadirachta indica A. Juss (‘neem’) and their derivatives were evaluated for their toxic action against fourth instar larvae of Aedes aegypti L. and Culex quinquefasciatus Say. Gedunin exhibited 100% toxic action against both the mosquito larvae at 50 and 10 ppm. Epoxyazadiradione and epoxynimolicinol also showed significant toxicities (≥50%) against larvae of both mosquito species at 50 ppm. These neem limonoids can have benefits in mosquito‐control programs.
Two New Unprecedented Acetonyl‐Bearing Sesquiterpenes from the Hainan Sponge Dysidea fragilis
Authors: Yu Zhi‐Guo , Li Jia , Li Zhen‐Yu , Guo Yue‐Wei
Published: June 2009

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Two new acetonyl‐bearing sesquiterpenes, dysifragilisins A and B (1 and 2, resp.), have been isolated from the Hainan marine sponge Dysidea fragilis. The structures of the new compounds were elucidated on the basis of detailed spectroscopic analyses and by comparison of their NMR data with those of structurally related compounds. A plausible biogenetic pathway is proposed for the origin of compounds 1 and 2.
Phenolic Constituents from Balanophora laxiflora with DPPH Radical‐Scavenging Activity
Authors: She Gai‐Mei , Zhang Ying‐Jun , Yang Chong‐Ren
Published: June 2009

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Balanophora laxiflora Hemsl. (Balanophoraceae), a dioeciously parasitic plant, has been used as a tonic and for sobering up from drunk by the local people of Yunnan province, China. The 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH) assay on the acetone extract of the fresh female plant of B. laxiflora displayed considerable radical‐scavenging activity (SC50=16.4 μg/ml). Further purification of the extract led to the isolation of two new phenolic glycosides, balaxiflorins A and B (1 and 2, resp.), together with 17 known phenolic compounds including 3‐phenylpropanoids, 3, 17–18, four lignans, 4–7, nine hydrolyzable tannins, 8–16, and gallic acid (19). Their structures were determined by detailed spectroscopic analysis. The free‐radical‐scavenging activity of the isolated compounds was examined by DPPH assay.
Flower and Root Oils of the Tunisian Daucus carota L. ssp. maritimus (Apiaceae): Integrated Analyses by GC, GC/MS, and 13C‐NMR Spectroscopy, and in vitro Antibacterial Activity
Authors: Jabrane Aymen , Jannet Hichem Ben , Harzallah‐Skhiri Féthia , Mastouri Maha , Casanova Joseph , Mighri Zine
Published: June 2009

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The essential oils from flowers and roots of Daucus carota L. ssp. maritimus were obtained by hydrodistillation and analyzed by combination of GC, GC/MS, and 13C‐NMR. The chemical composition of the flower and root oils of this subspecies is reported here for the first time. Thirty‐two and six compounds were identified in flower and root oils, respectively. A remarkable difference was found between the constituent percentages of the two organs. The chemical composition of the essential oil from flowers was characterized by a high proportion of monoterpene hydrocarbons (68.4%) and belonged to the sabinene (4; 51.6%) chemotype. The oxygenated monoterpenes represented the second major fraction of the same oil among which terpinen‐4‐ol (11.0%) was the predominant compound. Root oil exhibited a surprisingly different composition. Phenolic derivatives (76.3%), myristicin (31; 29.7%), and dillapiole (32; 46.6%) constituted the main fraction. The antibacterial effect resulted in the inhibition of a series of common human pathogenic bacteria, and of some clinically and environmentally isolated strains with significant MIC and MBC values.
Immunological Adjuvant Effect of a Water‐Soluble Polysaccharide, CPP, from the Roots of Codonopsis pilosula on the Immune Responses to Ovalbumin in Mice
Authors: Sun Yong‐Xu
Published: June 2009

In this study, one water‐soluble polysaccharide, CPP, was purified from the root of Codonopsis pilosula. The immunomodulatory effect and the adjuvant potential of CPP on the cellular and humoral immune response of ICR mice against ovalbumin (OVA) were investigated. CPP was shown not to be lethal in vivo for mice in doses ranging from 0.5 to 4 mg. ICR Mice were immunized subcutaneously with 0.1 mg of OVA alone or with 0.1 mg of OVA dissolved in saline‐containing aluminum hydroxide gel (Alum) (0.2 mg), QuilA (0.01 and 0.02 mg) or CPP (0.5, 1 or 2 mg) on days 1 and 15. Two weeks later (day 28), concanavalin A (ConA)‐, lipopolysaccharide (LPS)‐, and OVA‐stimulated splenocyte proliferation, and OVA‐specific serum antibodies were measured. CPP significantly enhanced the ConA‐, LPS‐, or OVA‐induced splenocyte proliferation in the OVA‐immunized mice especially at a dose of 1 mg (P<0.05 or P<0.01). The OVA‐specific IgG, IgG1, and IgG2b antibody levels in serum were also significantly enhanced by CPP compared with OVA control group (P<0.05 or P<0.01). The results suggest that CPP could be a safe efficacious adjuvant for use in vaccines against both pathogens and cancer.
Stemucronatoside L, a Pregnane Glycoside from the Roots of Stephanotis mucronata, Inhibits Th1/Th2 Immune Responses in vitro
Authors: Chen Feng‐Yang , Ye Yi‐Ping , Sun Hong‐Xiang , Li Xiao‐Yu , Shi Hong
Published: June 2009

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Stemucronatoside L (SML), isolated from Stephanotis mucronata, could suppress the activation of T cells in vitro. However, the mechanisms responsible for its immunosuppressive activity remain poorly understood. The purpose of this study was to investigate whether SML could suppress Th1/Th2 immune responses and to characterize the cellular mechanisms involved. Effects of SML on T‐lymphocyte subsets and the production of Th1 cytokines IL‐2 and IFN‐γ, and Th2 cytokines IL‐4 and IL‐10 from ConA‐stimulated mice splenocytes were detected by flow‐cytometric analysis and ELISA method, respectively. Furthermore, effects of SML on mRNA expression level of Th1/Th2 cytokines and transcription factors T‐bet and GATA‐3 were evaluated by RT‐PCR analysis. SML not only significantly decreased the percentage of CD4+ T cells and the CD4+/CD8+ ratio, but reduced the production of Th1/Th2 cytokines in a concentration‐dependent manner. The mRNA expression levels of Th1/Th2 cytokines and transcription factors (T‐bet and GATA‐3) were also suppressed by SML. These results suggested that SML could simultaneously inhibit Th1/Th2 immune responses by suppressing gene expression of Th1/Th2 cytokines and transcription factors.
Effective Insect Repellent Formulation in both Surfactantless and Classical Microemulsions with a Long‐Lasting Protection for Human Beings
Authors: Drapeau Jeremy , Verdier Marie , Touraud Didier , Kröckel Ulla , Geier Martin , Rose Andreas , Kunz Werner
Published: June 2009

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The aim of this work is to develop a new generation of repellent products with a long‐lasting protection based on a natural component, para‐menthane‐3,8‐diol (PMD). The active is first rendered soluble in a surfactantless microemulsion (H2O/iPrOH/PMD) and then in classical microemulsions. The presence of self‐associated nanostructures is detected by dynamic light scattering (DLS). A synergetic system of surfactants (Cremophor® RH40 and Texapon® N70) is used. Additionally, 2‐ethylhexane‐1,3‐diol and ethyl (−)‐(S)‐lactate are incorporated. The final product contains, as main components, 46% of H2O, 25% of iPrOH, 20% of non‐H2O‐soluble PMD, and only 4% of surfactants. Investigations of lasting protection on human volunteers are carried out using a cage test bioassay protocol and Aedes aegypti mosquitoes. A complete protection of 315 min is found on the test persons using the surfactantless microemulsion. An extension is observed with the final formulation to reach a mean of complete protection of 385 min. This study demonstrates that alternative formulations using a natural active instead of synthetic chemicals like N,N‐diethyl‐m‐methylbenzamide (DEET) can be efficient for human protection against mosquitoes.
Toward Safe Genetically Modified Organisms through the Chemical Diversification of Nucleic Acids
Authors: Herdewijn Piet , Marlière Philippe
Published: June 2009

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It is argued that genetic proliferation should be rationally extended so as to enable the propagation in vivo of additional types of nucleic acids (XNA for ‘xeno‐nucleic acids’), whose chemical backbone motifs would differ from deoxyribose and ribose, and whose polymerization would not interfere with DNA and RNA biosynthesis. Because XNA building blocks do not occur in nature, they would have to be synthesized and supplied to cells which would be equipped with an appropriate enzymatic machinery for polymerizing them. The invasion of plants and animals with XNA replicons can be envisioned in the long run, but it is in microorganisms, and more specifically in bacteria, that the feasibility of such chemical systems and the establishment of genetic enclaves separated from DNA and RNA is more likely to take place. The introduction of expanded coding through additional or alternative pairing will be facilitated by the propagation of replicons based on alternative backbone motifs and leaving groups, as enabled by XNA polymerases purposefully evolved to this end.
ICAT as a potential enhancer of monocytic differentiation: implications from the comparative proteome analysis of the HL60 cell line stimulated by all‐trans retinoic acid and NSC67657
Authors: Wang Weijia , Zhang Xiuming , Deng Kaiying , Huang Shifeng , Mao Xiaoqin , Fu Yurong , Yi Zhengjun , Yan Yurong , Qiu Zongyin
Published: June 2009

A novel sterol mesylate compound (NSC67657) was recently identified and reported by National Cancer Institute that could efficiently induce the differentiation of HL60 cells into monocytes in vitro and in vivo. The expression of many proteins would have been changed during the differentiation process, and some proteins may have played key roles in the differentiation of HL60 cell line induced by this drug. Therefore, we treated HL60 cells with NSC67657 and all‐trans retinoic acid (ATRA) to identify the differentially expressed proteins and determine their functions in cellular differentiation. Of the 45 differentially expressed protein spots investigated, 24 were either elevated or decreased in both the monocytic and granulocytic differentiating HL60 cells, 8 showed significant changes only when induced by NSC67657, and 13 showed significant changes only when induced by ATRA. After verification by RT‐PCR, Western blotting, and immunocytochemistry, only the protein ICAT was found to be elevated by NSC67657 treatment alone. Although the over‐expression of ICAT is not sufficient to induce the differentiation of HL60 cells into monocytes, it did increase the proportion of CD14+ cells in cells pretreated with NSC67657. Successful application of multiple techniques including two‐dimensional gel electrophoresis, matrix‐assisted laser desorption ionization time‐of‐flight mass spectrometry, Western blotting, and eukaryotic electroporation revealed that proteomic and molecular biological analyses provide valuable tools in drug development research. Copyright © 2009 John Wiley & Sons, Ltd.
Cover Picture: Analysis of Protein–Protein Interactions by Using Droplet‐Based Microfluidics (ChemBioChem 10/2009)
Authors: Srisa‐Art Monpichar , Kang Dong‐Ku , Hong Jongin , Park Hyun , Leatherbarrow Robin J. , Edel Joshua B. , Chang Soo‐Ik , deMello Andrew J.
Published: June 2009

The cover picture shows a segmented‐flow microfluidic system that was used to analyse protein–protein interactions in picolitre droplets. The 400 pL aqueous droplets were formed, encapsulated by a carrier fluid, and then transported through a 50 μm‐wide microchannel at a constant velocity. Each droplet contained fluorescently labelled antigens and antibodies, and FRET was used to report protein–protein interactions. Angiogenin (ANG), a small polypeptide implicated in angiogenesis and tumour growth, was selected as a model protein. Specifically, an anti‐ANG antibody (anti‐ANG Ab) and an ANG antigen were labelled with fluorophores to act as donor and acceptor in the FRET measurements. KD values for ANG and anti‐ANG Ab from these experiments (KD=6.4±1.6 nM) agree closely with data from bulk fluorescence polarisation measurements KD=9.0±1.5 nM). We expect that this novel experimental platform will have significant application in high‐throughput protein expression profiling and drug discovery. For further details, see the article by S.‐I. Chang, A. J. deMello et al. on p. 1605 ff.

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Retrograde recanalization of native coronary artery chronic occlusions via acutely occluded vein grafts
Authors: Brilakis Emmanouil S. , Banerjee Subhash , Lombardi William L.
Published: June 2009

Treatment of acutely occluded saphenous vein grafts may be challenging due to large thrombus burden and diffuse disease. We report two cases of thrombotic saphenous vein graft occlusion, in which after percutaneous attempts to recanalize the saphenous vein graft failed, the target native coronary artery chronic total occlusions were successfully treated using a retrograde approach. © 2009 Wiley‐Liss, Inc.
Changes in mitral regurgitation after transcatheter aortic valve implantation
Authors: Tzikas Apostolos , Piazza Nicolo , van Dalen Bas M. , Schultz Carl , Geleijnse Marcel L. , van Geuns Robert‐Jan , Galema Tjebbe W. , Nuis Rutger‐Jan , Otten Amber , Gutierrez‐Chico Juan‐Luis , Serruys Patrick W. , de Jaegere Peter P.
Published: June 2009

Objectives: To assess the acute and intermediate changes in mitral regurgitation (MR) severity after transcatheter aortic valve implantation (TAVI) with the CoreValve Revalving SystemTM (CRS). Background: Following surgical aortic valve replacement, improvement in MR is reported in 27–82% of the patients. The changes in MR severity following CRS implantation are unknown. Methods: Transthoracic echocardiography was performed in 79 consecutive patients before and after treatment, and at the first outpatient visit. Left ventricular dimensions and ejection fraction (LVEF), left atrial (LA) size, and aortic gradient were measured. MR was assessed by color flow mapping and was graded as none, mild, moderate, or severe. It was defined as organic or functional. The depth of CRS implantation was measured by angiography. Results: Post‐treatment, the mean gradient decreased from 48 ± 16 mm Hg to 9 ± 5 mm Hg (P < 0.0001). There was no significant change in the left ventricular dimensions, LA size, and LVEF. MR pretreatment was mild, moderate, or severe in 57%, 18%, and 1% of the patients, respectively. It was defined as organic in 27 patients (36%) and functional in 27 patients (36%). The degree of MR remained unchanged in 61% of the patients, improved in 17%, and worsened in 22%. MR improvement was associated with a lower baseline LVEF (P = 0.02). There was no association between the changes in MR severity and the depth of CRS implantation. Conclusions: Most patients who underwent TAVI had some degree of MR. Overall there was no change in the degree of MR post‐treatment. Patients in whom MR improved had a lower LVEF at baseline. © 2009 Wiley‐Liss, Inc.
Dirhodium(II) Compounds with Bridging Thienylphosphines: Studies on Reversible P,C/P,S Coordination
Authors: Lloret Julio , Estevan Francisco , Lahuerta Pascual , Hirva Pipsa , Pérez‐Prieto Julia , Sanaú Mercedes
Published: June 2009

Monocyclometalated compound [Rh2{(C8H4S)P(C8H5S)2}(CH3CO2H)2(O2CCH3)3] (1 a) and bis‐cyclometalated compound [Rh2{(C8H4S)P(C8H5S)2}2(CH3CO2H)2(O2CCH3)2] (2 a) have been isolated from the reaction of dirhodium tetraacetate and tris(2‐benzo[b]thienyl)phosphine (2 BTP) using low acidic solutions. By contrast, in pure acetic acid the reaction of Rh2(O2CCH3)4 with 2 BTP and tris(2‐thienyl)phosphine (2 TP), followed by replacement of the axial acetate ligands by chlorides, led to [Rh2{(2‐C8H5S)P(2‐C8H5S)2}2Cl2(O2CCH3)2] (3 b) and [Rh2{(2‐C4H3S)P(C4H3S)2}2Cl2(O2CCH3)2] (5 b), respectively. These new dirhodium(II) compounds possess equatorial bridging ligands in a phosphorous–sulfur (P,S) coordination mode. The reversible switching between the P,C and P,S bonding mode of the phosphine has been studied in the monocyclometalated [Rh2{(C4H2S)P(C4H3S)2}(CH3CO2H)2(O2CCH3)3] (6 a), which was selectively transformed into compound [Rh2{(2‐C4H3S)P(C4H3S)2}(CF3SO3)(CH3CO2H)(O2CCH3)3] (7 c) in triflic acid media. Remarkably, compound 7 c reverts to the starting compound 6 a upon treatment with sodium acetate. Theoretical DFT calculations for both the P,C/P,S rearrangement and the base‐promoted reversion have been performed to explain the experimental findings. Data suggest the P,C/P,S rearrangement occurs by means of a “concerted protonation–demetalation mechanism” followed by η2 coordination of the thienyl ring and subsequent isomerization to the S‐η1‐coordination mode. In the reversion reaction, the base coordinated at the axial position would promote a concerted metalation–deprotonation mechanism.
Synthesis, Conformational Interconversion, and Photophysics of Tethered Porphyrin–Fullerene Dyads with Parachute Topology
Authors: Fazio Michael A. , Durandin Alexander , Tkachenko Nikolai V. , Niemi Marja , Lemmetyinen Helge , Schuster David I.
Published: June 2009

The synthesis of a porphyrin–fullerene dyad with “parachute” topology is reported. To determine whether the dyad is “flexing” at room temperature, low‐temperature NMR experiments were used. Computational modeling has shown the low‐energy conformation of the dyad to be nonsymmetric. Although, 1H NMR spectroscopy at room temperature is consistent with a molecule with C2v symmetry, the spectrum changes on lowering the temperature consistent with “windshield wiper”‐like motion, in which the porphyrin moiety rotates from one side of the C60 sphere to the other. Nanosecond and picosecond fluorescence lifetime experiments show two components contribute to the fluorescence decay, also consistent with the presence of more than one conformer.
Trisilyl‐Substituted Vinyl Cations
Authors: Klaer Andrea , Syha Yvonne , Nasiri Hamid Reza , Müller Thomas
Published: June 2009

A series of β,β‐disilyl‐substituted vinyl cations were prepared by intramolecular addition of transient silylium ions to CC triple bonds. The vinyl cations were isolated from hydrocarbon solutions as tetrakis(pentafluorophenyl) borates at room temperature. The substituents directly attached to the positively charged carbon atom were varied from tert‐butyl‐ to trialkylsilyl‐ to trialkylgermyl groups. The cations were identified by their characteristic 13C and 29Si NMR data. The NMR investigations revealed for β,β‐disilyl‐α‐germyl‐ and trisilyl‐substituted vinyl cations a highly dynamic structure in which both vinylic carbon atoms undergo an intramolecular exchange process which is fast on the NMR time scale at room temperature. NMR studies using a doubly 13C‐labeled vinyl cation suggest as mechanism for this exchange process a rotation of the dicarbyne CC2− unit within the triangle defined by the three cationic silyl fragments. Therefore the dynamic structure indicated for trisilyl‐ or disilylgermyl‐substituted vinyl cations parallels the situation found for the parent vinyl cation, the protonated acetylene.
Cooperative Acid–Base Effects with Functionalized Mesoporous Silica Nanoparticles: Applications in Carbon–Carbon Bond‐Formation Reactions
Authors: Shylesh Sankaranarayanapillai , Wagner Alex , Seifert Andreas , Ernst Stefan , Thiel Werner R.
Published: June 2009

Acid–base bifunctional mesoporous silica nanoparticles (MSN) were prepared by a one‐step synthesis by co‐condensation of tetraethoxysilane (TEOS) and silanes possessing amino and/or sulfonic acid groups. Both the functionality and morphology of the particles can be controlled. The grafted functional groups were characterized by using solid‐state 29Si and 13C cross‐polarization/magic angle spinning (CP/MAS) NMR spectroscopy, thermal analysis, and elemental analysis, whereas the structural and the morphological features of the materials were evaluated by using XRD and N2 adsorption–desorption analyses, and SEM imaging. The catalytic activities of the mono‐ and bifunctional mesoporous hybrid materials were evaluated in carbon–carbon coupling reactions like the nitroaldol reaction and the one‐pot deacetalization–nitroaldol and deacetalization–aldol reactions. Among all the catalysts evaluated, the bifunctional sample containing amine and sulfonic acid groups (MSN–NNH2–SO3H) showed excellent catalytic activity, whereas the homogeneous catalysts were unable to initiate the reaction due to their mutual neutralization in solution. Therefore a cooperative acid–base activation is envisaged for the carbon–carbon coupling reactions.
Structure and Bonding in Neutral and Cationic 14‐Electron Gold Alkyne π Complexes
Authors: Flügge Susanne , Anoop Anakuthil , Goddard Richard , Thiel Walter , Fürstner Alois
Published: June 2009

Cyclododecyne (5) as a prototype unstrained alkyne was coordinated to either the neutral [AuCl] fragment or to two different cationic [Au(NHC)]+ entities (NHC=N‐heterocyclic carbene), and the resulting complexes 6, 8, and 10 were characterized by X‐ray crystallography and NMR spectroscopy. Since the structure of cyclododecyne in the solid state could also be obtained after in situ crystallization, a comparison was possible that provides insights into structural changes imposed on the alkyne by the different gold fragments. These data are interpreted on the basis of a DFT analysis of the bonding situation in the individual compounds, which provides insights into the very first elementary step common to many gold‐catalyzed transformations.
Cover Picture: Synthesis and Reactivity of Functionalized Binary and Ternary Thiometallate Complexes [(RT)4S6], [(RSn)3S4]2−, [(RT)2(CuPPh3)6S6], and [(RSn)6(OMe)6Cu2S6]4− (R=C2H4COOH, CMe2CH2COMe; T=Ge, Sn) (Chem. Eur. J. 27/2009)
Authors: Fard Zohreh Hassanzadeh , Xiong Lin , Müller Christian , Hołyńska Małgorzata , Dehnen Stefanie
Published: June 2009

Proof‐of‐principle is reported for a directed functionalization and derivatization of chalcogenidometallate cages with respect to the formation of hybrid compounds containing (M)/T/E semi‐conductor nodes (M=Cu; T=Ge, Sn; E=S). In their Full Paper on page 6595 ff., S. Dehnen et al. show how it is possible to generate functionalized ternary CuSnS or CuGeS clusters and to transfer COMe ligands into CR(N–NH2) or CR(N–NHPh) terminal groups by reaction of a series of novel, functionalized thiometallate cages [(RT)nSm] (n/m=4/6, 3/4), the R ligands of which are terminated by COO(H) or COMe.

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ChemInform Abstract: Structure and Stability of Water Chains (H2O)n, n = 5—20
Authors: Parthasarathi R. , Elango M. , Subramanian V. , Sathyamurthy N.
Published: June 2009

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Probing the Electronic and Structural Properties of the Niobium Trimer Cluster and Its Mono‐ and Dioxides: Nb3On‐ and Nb3On (n = 0—2)
Authors: Zhai Hua‐Jin , Wang Bin , Huang Xin , Wang Lai‐Sheng
Published: June 2009

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Inhomogeneous 2D Linear Intergrowth Structures Among Novel Y—Cu—Mg Ternary Compounds with Yttrium/Copper Equiatomic Ratio.
Authors: Solokha Pavlo , De Negri Serena , Pavlyuk Volodymyr , Saccone Adriana
Published: June 2009

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: New Titanium Hydroxyfluoride Ti0.75(OH)1.5F1.5 as a UV Absorber.
Authors: Demourgues A. , Penin N. , Durand E. , Weill F. , Dambournet D. , Viadere N. , Tressaud A.
Published: June 2009

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Synthesis, Crystal Structure, and Magnetic Properties of K4Mn3(HPO4)4 (H2PO4)2.
Authors: Feng Dawei , Wang Cheng , Cheng Wentai , Li Guobao , Tian Shujian , Liao Fuhui , Xiong Ming , Lin Jianhua
Published: June 2009

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Linking Structural Dynamics and Functional Diversity in Asymmetric Catalysis.
Authors: Nojiri Akihiro , Kumagai Naoya , Shibasaki Masakatsu
Published: June 2009

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Direct Enantioselective Aldol Reactions Catalyzed by a Proline—Thiourea Host—Guest Complex.
Authors: Reis Oemer , Eymur Serkan , Reis Barbaros , Demir Ayhan S.
Published: June 2009

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Gold‐Catalyzed [4C + 3C] Intramolecular Cycloaddition of Allenedienes: Synthetic Potential and Mechanistic Implications.
Authors: Trillo Beatriz , Lopez Fernando , Montserrat Sergi , Ujaque Gregori , Castedo Luis , Lledos Agusti , Mascarenas Jose L.
Published: June 2009

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.