bluuebunny/crossref_metadata_2025 huggingface dataset:
The levosimendan metabolite OR‐1896 elicits vasodilation by activating the KATPand BKCachannels in rat isolated arterioles
Authors: Erdei Nóra , Papp Zoltán , Pollesello Piero , Édes István , Bagi Zsolt
Published: May 2006

We characterized the vasoactive effects of OR‐1896, the long‐lived metabolite of the inodilator levosimendan, in coronary and skeletal muscle microvessels.

The effect of OR‐1896 on isolated, pressurized (80 mmHg) rat coronary and gracilis muscle arteriole (∼150 μm) diameters was investigated by videomicroscopy.

OR‐1896 elicited concentration‐dependent (1 nM–10 μM) dilations in coronary (maximal dilation: 66±6%, relative to that in Ca2+‐free solutions; pD2: 7.16±0.42) and gracilis muscle arterioles (maximal dilation: 73±4%; pD2: 6.71±0.42), these dilations proving comparable to those induced by levosimendan (1 nM–10 μM) in coronary (maximal dilation: 83±6%; pD2: 7.06±0.14) and gracilis muscle arterioles (maximal dilation: 73±12%; pD2: 7.05±0.1).

The maximal dilations in response to OR‐1896 were significantly (P<0.05) attenuated by the nonselective K+channel inhibitor tetraethylammonium (1 mM) in coronary (to 34±9%) and gracilis muscle arterioles (to 28±6%).

Glibenclamide (5 or 10 μM), a selective ATP‐sensitive K+channel (KATP) blocker, elicited a greater reduction of OR‐1896‐induced dilations in skeletal muscle arterioles than in coronary microvessels.

Conversely, the selective inhibition of the large conductance Ca2+‐activated K+channels (BKCa) with iberiotoxin (100 nM) significantly reduced the OR‐1896‐induced maximal dilation in coronary arterioles (to 21±6%), but was ineffective in skeletal muscle arterioles (72±8%).

Accordingly, OR‐1896 elicits a substantial vasodilation in coronary and skeletal muscle arterioles, by activating primarily BKCaand KATPchannels, respectively, and it is suggested that OR‐1896 contributes to the long‐term hemodynamic effects of levosimendan.

British Journal of Pharmacology(2006)148, 696–702. doi:10.1038/sj.bjp.0706781
Sterol and lipid trafficking in mammalian cells
Authors: Maxfield F.R. , Mondal M.
Published: May 2006

The pathways involved in the intracellular transport and distribution of lipids in general, and sterols in particular, are poorly understood. Cholesterol plays a major role in modulating membrane bilayer structure and important cellular functions, including signal transduction and membrane trafficking. Both the overall cholesterol content of a cell, as well as its distribution in specific organellar membranes are stringently regulated. Several diseases, many of which are incurable at present, have been characterized as results of impaired cholesterol transport and/or storage in the cells. Despite their importance, many fundamental aspects of intracellular sterol transport and distribution are not well understood. For instance, the relative roles of vesicular and non-vesicular transport of cholesterol have not yet been fully determined, nor are the non-vesicular transport mechanisms well characterized. Similarly, whether cholesterol is asymmetrically distributed between the two leaflets of biological membranes, and if so, how this asymmetry is maintained, is poorly understood. In this review, we present a summary of the current understanding of these aspects of intracellular trafficking and distribution of lipids, and more specifically, of sterols.
Nucleus–vacuole junctions in yeast: anatomy of a membrane contact site
Authors: Kvam E. , Goldfarb D.S.
Published: May 2006

NV junctions (nucleus–vacuole junctions) in Saccharomyces cerevisiae are MCSs (membrane contact sites) formed through specific interactions between Vac8p on the vacuole membrane and Nvj1p in the outer nuclear membrane, which is continuous with the perinuclear ER (endoplasmic reticulum). NV junctions mediate a unique autophagic process that degrades portions of the yeast nucleus through a process called ‘piecemeal microautophagy of the nucleus’ (PMN). Our studies suggest that the lipid composition of NV junctions plays an important role in the biogenesis of PMN structures. NV junctions represent a unique model system for studying the biology of ER MCSs, as well as the molecular mechanism of selective microautophagy.
MLN64 and MENTHO, two mediators of endosomal cholesterol transport
Authors: Alpy F. , Tomasetto C.
Published: May 2006

MLN64 (metastatic lymph node 64) and MENTHO (MLN64 N-terminal homologue) are two late-endosomal proteins that share a conserved region of four transmembrane helices with three short intervening loops called the MENTAL domain (MLN64 N-terminal domain). This domain mediates MLN64 and MENTHO homo- and hetero-interactions, targets both proteins to late endosomes and binds cholesterol in vivo. In addition to the MENTAL domain, MLN64 contains a cholesterol-specific START domain [StAR (steroidogenic acute regulatory protein)-related lipid transfer domain]. The START domain is a protein module of approx. 210 residues that binds lipids, including sterols, and is present in 15 distinct proteins in mammals. Thus MLN64 and MENTHO define discrete cholesterol-containing subdomains within the membrane of late endosomes where they may function in cholesterol transport. The MENTAL domain might serve to maintain cholesterol at the membrane of late endosomes prior to its shuttle to cytoplasmic acceptor(s) through the START domain.
Sterol trafficking between the endoplasmic reticulum and plasma membrane in yeast
Authors: Sullivan D.P. , Ohvo-Rekilä H. , Baumann N.A. , Beh C.T. , Menon A.K.
Published: May 2006

We recently showed that transport of ergosterol from the ER (endoplasmic reticulum) to the sterol-enriched PM (plasma membrane) in yeast occurs by a non-vesicular (Sec18p-independent) mechanism that results in the equilibration of sterol pools in the two organelles [Baumann, Sullivan, Ohvo-Rekilä, Simonot, Pottekat, Klaassen, Beh and Menon (2005) Biochemistry 44, 5816–5826]. To explore how this occurs, we tested the role of proteins that might act as sterol transporters. We chose to study oxysterol-binding protein homologues (Osh proteins), a family of seven proteins in yeast, all of which contain a putative sterol-binding pocket. Recent structural analyses of one of the Osh proteins [Im, Raychaudhuri, Prinz and Hurley (2005) Nature (London) 437, 154–158] suggested a possible transport cycle in which Osh proteins could act to equilibrate ER and PM pools of sterol. Our results indicate that the transport of newly synthesized ergosterol from the ER to the PM in an OSH deletion mutant lacking all seven Osh proteins is slowed only 5-fold relative to the isogenic wild-type strain. Our results suggest that the Osh proteins are not sterol transporters themselves, but affect sterol transport in vivo indirectly by affecting the ability of the PM to sequester sterols.
Uptake and trafficking of exogenous sterols in Saccharomyces cerevisiae
Authors: Raychaudhuri S. , Prinz W.A.
Published: May 2006

The proper distribution of sterols among organelles is critical for numerous cellular functions. How sterols are sorted and moved among membranes remains poorly understood, but they are transported not only in vesicles but also by non-vesicular pathways. One of these pathways moves exogenous sterols from the plasma membrane to the endoplasmic reticulum in the yeast Saccharomyces cerevisiae. We have found that two classes of proteins play critical roles in this transport, ABC transporters (ATP-binding-cassette transporters) and oxysterol-binding protein-related proteins. Transport is also regulated by phosphoinositides and the interactions of sterols with other lipids. Here, we summarize these findings and speculate on the role of non-vesicular sterol transfer in determining intracellular sterol distribution and membrane function.
Lipid homoeostasis and Golgi secretory function
Authors: Lev S.
Published: May 2006

The unique lipid composition of the Golgi membranes is critical for maintaining their structural and functional identity, and is regulated by local lipid metabolism, a variety of lipid-binding, -modifying, -sensing and -transfer proteins, and by selective lipid sorting mechanisms. A growing body of evidence suggests that certain lipids, such as phosphoinositides and diacylglycerol, regulate Golgi-mediated transport events. However, their exact role in this process, and the underlying mechanisms that maintain their critical levels in specific membrane domains of the Golgi apparatus, remain poorly understood. Nevertheless, recent advances have revealed key regulators of lipid homoeostasis in the Golgi complex and have demonstrated their role in Golgi secretory function.
Organization and functions of sphingolipid biosynthesis in yeast
Authors: Riezman H.
Published: May 2006

Sphingolipids are important signalling molecules and thus it is very important to understand how they are generated. Sphingolipid biosynthesis shows a conserved compartmentalization in eukaryotic cells. Their synthesis begins in the endoplasmic reticulum and is completed in the Golgi apparatus. We now know quite a bit about the topology of the reactions in the pathway, but certain critical steps, such as ceramide synthesis, are still poorly understood. In the present paper, we discuss the latest views on this subject.
Endoplasmic reticulum generates calcium signalling microdomains around the nucleus and spindle in syncytial Drosophila embryos
Authors: Parry H. , McDougall A. , Whitaker M.
Published: May 2006

Cell cycle calcium signals are generated by inositol trisphosphate-mediated release of calcium from internal stores [Ciapa, Pesando, Wilding and Whitaker (1994) Nature (London) 368, 875–878; Groigno and Whitaker (1998) Cell 92, 193–204]. The major internal calcium store is the ER (endoplasmic reticulum): the spatial organization of the ER during mitosis is important in defining a microdomain around the nucleus and mitotic spindle in early Drosophila embryos [Parry, McDougall and Whitaker (2005) J. Cell Biol. 171, 47–59]. Nuclear divisions in syncytial Drosophila embryos are accompanied by both cortical and nuclear localized calcium transients. Mitosis is prevented by the InsP3 antagonists Xestospongin C and heparin. Nuclear-localized transients and cortical transients rely on extraembryonic calcium, suggesting that ER calcium levels are maintained by calcium influx.
Endosomal cholesterol traffic: vesicular and non-vesicular mechanisms meet
Authors: Hölttä-Vuori M. , Ikonen E.
Published: May 2006

The endoplasmic reticulum is traditionally perceived as the key compartment for regulating intracellular cholesterol metabolism. Increasing evidence suggests that the endocytic pathway provides an additional regulatory level governing intracellular cholesterol trafficking and homoeostasis. Sterols can enter, and apparently also exit, endosomal compartments via both vesicular and non-vesicular mechanisms. A number of studies have focused on endosomal sterol removal as its defects lead to cholesterol storage diseases. So far, the bulk of evidence on endosomal sterol egress describes the involvement of membrane trafficking machineries. Interestingly, two late endosomal sterol-binding proteins were recently shown to regulate the movement of late endosomes along cytoskeletal tracks. These studies provide the first indications of how non-vesicular and vesicular mechanisms may co-operate in endosomal sterol trafficking.
Lipid trafficking between the endoplasmic reticulum and the chloroplast
Authors: Awai K. , Xu C. , Lu B. , Benning C.
Published: May 2006

The photosynthetic (thylakoid) membrane of plants is one of the most extensive biological cell membrane systems found in Nature. It harbours the photosynthetic apparatus, which is essential to life on Earth as carbon dioxide is fixed and atmospheric oxygen released by photosynthesis. Lipid biosynthetic enzymes of different subcellular compartments participate in the biogenesis of the thylakoid membrane system. This process requires the extensive exchange of lipid precursors between the chloroplast and the ER (endoplasmic reticulum). The underlying lipid trafficking phenomena are not yet understood at the mechanistic level, but genetic mutants of the model plant Arabidopsis thaliana with disruptions in lipid trafficking between the ER and the chloroplast have recently become available. Their study has led to the identification of components of the lipid transfer machinery at the inner chloroplast envelope.
Lipid dynamics in neurons
Authors: Vance J.E. , Karten B. , Hayashi H.
Published: May 2006

Compared with other organs, the brain is highly enriched in cholesterol. Essentially all cholesterol in the brain is synthesized within the brain; the blood–brain barrier prevents the import of plasma lipoproteins into the brain. Consequently, the brain operates an independent lipoprotein transport system in which glial cells produce ApoE (apolipoprotein E)-containing lipoproteins that are thought to deliver cholesterol to neurons for axonal growth and repair. We have shown that ApoE-containing lipoproteins generated by glial cells stimulate axon extension. ApoE associated with lipoprotein particles, and a receptor of the low-density lipoprotein receptor family, are required for stimulation of axon growth. NPC (Niemann–Pick type C) disease is a severe neurological disorder caused by mutations in the NPC1 or NPC2 gene. A hallmark of this disease is impaired transport of cholesterol out of late endosomes/lysosomes and the accumulation of cholesterol in these organelles. Although cholesterol accumulates in cell bodies of neurons from NPC1-deficient mice, the cholesterol content of axons is reduced. The presence of NPC1 in endosomal structures in nerve terminals, and the finding of aberrant synaptic vesicles, suggest that defects in synaptic vesicle recycling contribute to neurological abnormalities characteristic of NPC disease. We have also shown that ApoE-containing lipoproteins produced by glial cells from NCP1-deficient mice are of normal composition and stimulate axon extension.
Cytokines and proteoglycans: an introductory overview
Authors: Mulloy B. , Rider C.C.
Published: May 2006

The defining characteristic of the glycoproteins known as proteoglycans is the presence of O-linked acidic polysaccharides known as GAGs (glycosaminoglycans). The backbone of these linear polysaccharides is a repeating disaccharide, comprising N-acetyl hexosamine alternating with β-D-glucuronic acid, α-L-iduronic acid, or galactose. For some GAGs, partial deacetylation, epimerization of glucuronic acid, and substitution with N- and O-sulphates result in highly complex, heterogeneous structures. The interactions with proteins through which GAGs exert their biological effects depend on the resulting sequences. Some proteins, for example antithrombin, have highly specific sequence requirements for their GAG ligand [in this case heparin or HS (heparan sulphate)]; others, for example the fibroblast growth factors, are less demanding. GAGs, in particular HS, play a role as co-receptors for some cytokines. In addition, HS is thought to be important for the localization of cytokines, acting both as a tissue store and as a mediator of morphogen gradient formation in development. The structural determinants of GAG–cytokine interactions are therefore clearly important to understanding the biology of development, wound healing and the immune system. No single paradigm has been identified for such interactions, and the search for general principles underlying involvement of GAGs in cytokine function is at an early stage.
Signalling by HGF/SF and Met: the role of heparan sulphate co-receptors
Authors: Kemp L.E. , Mulloy B. , Gherardi E.
Published: May 2006

The receptor tyrosine kinase Met and its ligand HGF/SF (hepatocyte growth factor/scatter factor) are essential in the signalling pathways required for embryogenesis and tissue regeneration. Aberrant signalling of this complex is also a feature of many tumours and appears to contribute to the growth, invasiveness and metastasis of both carcinomas and sarcomas. HGF/SF, like many other angiogenic growth factors, employs heparan sulphate as co-receptor. The role of this interaction has not been completely defined but appears to be physiologically relevant. Thus the presence of heparin increases the potency of HGF/SF in experiments with cells in culture leading to elevated downstream signalling effects and, although not vital for the Met–HGF/SF interaction, heparin or heparan sulphate is essential for the activity of certain isoforms of HGF/SF, such as NK1 and NK2. Here, we summarize the progress made in understanding the interaction between heparin and heparan sulphate and NK1, NK2 and HGF/SF and we discuss their role in HGF/SF–Met signalling.
Interaction of the guidance molecule Slit with cellular receptors
Authors: Hohenester E. , Hussain S. , Howitt J.A.
Published: May 2006

Slits are large secreted glycoproteins characterized by an unusual tandem of four LRR (leucine-rich repeat) domains in their N-terminal half. Slit proteins were initially described as repulsive guidance cues in neural development, but it has become clear that they have additional important functions, for instance in the vasculature and immune system. Genetic studies have identified two types of cellular receptors for Slits: Robos (Roundabout) and the HS (heparan sulphate) proteoglycan syndecan. The intracellular signalling cascade downstream of Robo activation is slowly being elucidated, but the mechanism of transmembrane signalling by Robo has remained obscure. No active signalling role for syndecan has yet been demonstrated. Slit–HS interactions may be important for shaping the presumed Slit gradient or presenting Slit at its target cell surface. Recent studies have mapped the binding sites for Robos and HS/heparin to discrete Slit domains. Robos bind to the second LRR domain of Slit, whereas HS/heparin binds with very high affinity to the C-terminal portion of Slit. Slit activity is likely to be modulated by physiological proteolytic cleavage in the region separating the Robo and HS/heparin-binding sites.
Developing chemokine mutants with improved proteoglycan affinity and knocked-out GPCR activity as anti-inflammatory recombinant drugs
Authors: Potzinger H. , Geretti E. , Brandner B. , Wabitsch V. , Piccinini A.-M. , Rek A. , Kungl A.J.
Published: May 2006

The interaction of chemokines and GAGs (glycosaminoglycans) on endothelial surfaces is a crucial step for establishing a chemotactic gradient which leads to the functional presentation of chemokines to their GPCRs (G-protein-coupled receptors) and thus to activation of approaching leucocytes. Based on molecular modelling, biophysical investigations, cell-based and in vivo experiments, we have developed a novel concept for therapeutically interfering with chemokine–GAG interactions, namely dominant-negative chemokine mutants with improved GAG binding affinity and knocked-out GPCR activity. These recombinant proteins displace their wild-type chemokine counterparts from the natural proteoglycan co-receptors without being able to activate leucocytes via GPCRs. Our mutant chemokines therefore represent the first protein-based GAG antagonists with high therapeutic potential in inflammatory diseases.
Multiprotein signalling complexes: regional assembly on heparan sulphate
Authors: Gallagher J.T.
Published: May 2006

Heparan sulphate (HS) is an abundant component of cell surfaces and the extracellular matrix. It binds to a wide variety of peptide growth factors, morphogens, chemokines and extracellular matrix proteins (e.g. fibronectin) and many of these interactions are essential for these effector proteins to transduce signals across the plasma membrane. The unique molecular design and flexibility of HS are essential for its ability to exert control over the cellular response to proteinaceous ligands. The clustering of sulphated sugar residues in a series of complex domains with variable sulphation patterns generates considerable diversity in the molecular fine structure of HS. This diversity reflects a high degree of selectivity in protein recognition and in the assembly of functional multiprotein complexes on the HS polymer chain.
Insights into the role of heparan sulphate in fibroblast growth factor signalling
Authors: Harmer N.J.
Published: May 2006

Signalling from the FGFs (fibroblast growth factors) is crucial for the correct development and homoeostasis of a wide range of cells and tissues. The FGF/FGFR (FGF receptor) signalling system forms an important paradigm for HS (heparan sulphate)-binding proteins, as both the growth factor and receptor bind to HS, and HS or heparin is an absolute requirement for full signalling. The FGF signalling system has been extremely well structurally characterized, and details of each interaction involved in forming a ternary complex of FGF–FGFR–heparin have been elucidated. Recent work has focused on a more thorough understanding of the nature of the FGF–heparin complex in particular, demonstrating that FGFs preferentially bind to similar sites on the co-receptor, and that FGF–FGFR pairs show greater specificity for heparin sulphation patterns than individual FGFs. Further work has suggested that FGF–FGFR–heparin signalling complexes contain one molecule of heparin only, and that when longer fragments of heparin are used to form FGF–FGFR–heparin complexes, multiple complexes form upon the saccharide. These observations form the basis of a model where the range of interactions that FGFs and FGFRs can form with one another and with HS may lead to the formation of complexes with more than two FGFR units. Therefore HS will be crucial to FGF signalling from the initial signalling event to the formation of large receptor clusters.
TSG-6: a pluripotent inflammatory mediator?
Authors: Milner C.M. , Higman V.A. , Day A.J.
Published: May 2006

TSG-6 is a multifunctional protein that is up-regulated in many pathological and physiological contexts, where it plays important roles in inflammation and tissue remodelling. For example, it is a potent inhibitor of neutrophil migration and can modulate the protease network through inhibition of plasmin. TSG-6 binds a wide range of GAGs (glycosaminoglycans) [i.e. HA (hyaluronan), chondroitin 4-sulphate, dermatan sulphate, heparin and heparan sulphate] as well as a variety of protein ligands, where these interactions can influence the activities of TSG-6. For example, through its association with HA, TSG-6 can mediate HA cross-linking via several different mechanisms, some of which promote leucocyte adhesion. Binding to heparin, however, enhances the ability of TSG-6 to potentiate the anti-plasmin activity of inter-α-inhibitor, which binds non-covalently to TSG-6 via its bikunin chain. Furthermore, although HA and heparin interact with distinct sites on the Link module, the binding of heparin can inhibit subsequent interaction with HA. In addition, the interactions of TSG-6 with HA, heparin and at least some of its protein ligands are sensitive to pH. Therefore it seems that in different tissue micro-environments (characterized, for example, by pH and GAG content), TSG-6 could be partitioned into functional pools with distinct activities.
Heparan sulphate requirement in platelet-derived growth factor B-mediated pericyte recruitment
Authors: Kurup S. , Abramsson A. , Li J.P. , Lindahl U. , Kjellen L. , Betsholtz C. , Gerhardt H. , Spillmann D.
Published: May 2006

HS (heparan sulphate) plays a key role in angiogenesis, by interacting with growth factors required in the process. It has been proposed that HS controls the diffusion, and thus the availability, of platelet-derived growth factor B that is needed for pericyte recruitment around newly formed capillaries. The present paper summarizes our studies on the importance of HS structure in this regulatory process.
Basic fibroblast growth factor: an extracellular mechanotransducer in articular cartilage?
Authors: Vincent T. , Saklatvala J.
Published: May 2006

Mechanical stimuli are important signals in articular cartilage, but what mediates them is unknown. We have shown that extracellular-signal-regulated kinase was activated on cutting and loading articular cartilage, and deduced that this was due to the release of bFGF (basic fibroblast growth factor) from the tissue. bFGF was shown to be extracellular, and by immunohistochemistry, was present in the pericellular matrix of articular chondrocytes attached to the heparan sulphate proteoglycan perlecan. We propose a novel mechanotransduction model, whereby pericellular bFGF, a short distance from the cell surface, becomes available to the cell surface tyrosine kinase receptors when articular cartilage is loaded.
Interferon and heparan sulphate
Authors: Lortat-Jacob H.
Published: May 2006

In 1954, substances that protected cells from viral infection were discovered and named IFN (interferon). This family of cytokines, which were the first to be used in clinical therapy, is classified into type I and II IFNs. Type I mainly consists of IFNα and IFNβ subtypes, which are structurally related and bind to a common receptor. IFNγ, the sole type II IFN, is structurally unrelated, binds to a different receptor and, as a dimer, strongly interacts with HS (heparan sulphate). In addition to its antiviral activity, it modulates nearly all phases of immune and inflammatory responses. IFNγ binding to HS controls the blood clearance, the subsequent tissue targeting and the local accumulation of the cytokine. It also regulates IFNγ activity by a unique mechanism involving a controlled processing of the C-terminal peptide. The binding site encompasses an N-acetylated glucosamine-rich domain separating two highly sulphated sequences that each binds to one IFNγ monomer. Based on this template, a set of glycoconjugate mimetics that would mimic the IFNγ binding site has been synthesized. One of these molecules displays high affinity for the cytokine and inhibits binding to both HS and IFNγR (IFNγ receptor), the cell-surface receptor. These results validate the HS structural determinants for IFNγ recognition, and provide a new strategy to inhibit IFNγ in a number of diseases in which the cytokine has been identified as a target.
Infrared multiphoton spectra from metal dication complexes in the gas phase
Authors: Wu Guohua , Guan Jingang , Aitken Georgina D. C. , Cox Hazel , Stace Anthony J.
Published: May 2006

Infrared multiphoton spectra have been recorded for the first time from metal dication complexes held in an ion trap. The photofragmentation of [M(pyridine)4]2+ complexes has been observed in the range 920–1090cm−1 and for M=Cu2+, Mg2+ and Zn2+. The narrow absorption features are identified as vibrational modes of the pyridine molecule and comparisons with calculations suggest that the Mg2+ and Zn2+ ion complexes have D2d (compressed tetrahedron) structures, and that the Cu2+ complex is probably square-planar (D4h).
A femtosecond study of excitation wavelength dependence of solvation dynamics in a PEO-PPO-PEO triblock copolymer micelle
Authors: Sen Pratik , Ghosh Subhadip , Sahu Kalyanasis , Mondal Sudip Kumar , Roy Durba , Bhattacharyya Kankan
Published: May 2006

Excitation wavelength (λex) dependence of solvation dynamics of coumarin 480 (C480) in the micellar core of a water soluble triblock copolymer, PEO20-PPO70-PEO20 (Pluronic P123), is studied by femtosecond and picosecond time resolved emission spectroscopies. In the P123 micelle, the width of the emission spectrum of C480 is found to be much larger than that in bulk water. This suggests that the P123 micelle is more heterogeneous than bulk water. The steady state emission maximum of C480 in P123 micelle shows a significant red edge excitation shift by 25nm from 453nm at λex=345nmto478nm at λex=435nm. The solvation dynamics in the interior of the triblock copolymer micelle is found to depend strongly on the excitation wavelength. The excitation wavelength dependence is ascribed to a wide distribution of locations of C480 molecules in the P123 micelle with two extreme environments—a bulklike peripheral region with very fast solvent response and a very slow core region. With increase in λex, contribution of the bulklike region having an ultrafast component (⩽2ps) increases from 7% at λex=375nm to 78% at λex=425nm while the contribution of the ultraslow component (4500ps) decreases from 79% to 17%.
Microwave and theoretical investigation of the internal rotation in m-cresol
Authors: Hellweg Arnim , Hättig Christof , Merke Ilona , Stahl Wolfgang
Published: May 2006

The microwave spectrum of m-cresol (3-methylphenol) has been investigated using a molecular beam Fourier transform microwave spectrometer in the frequency range from 3to26.5GHz. The rotation of the hydroxy group into two different unequal energetic minima leads to different spectra for the syn- and anticonformers. Because of a high potential barrier both conformers can be analyzed independently. The methyl group is undergoing an almost free internal rotation which is only hindered by small barriers and splits the vibrational ground state in two states of internal rotation denoted as A and E species. The spacing between the species is found to be up to 10GHz. The potential for the internal rotation can be determined from the spectra and analyzed in terms of the Fourier components V3 and V6. For syn-m-cresol these parameters were determined as V3=673(3)GHz and V6=−335(24)GHz and for anti-m-cresol V3=95(5)GHz and V6=−416(46)GHz. The barriers to internal rotation were furthermore calculated with second-order Møller-Plesset perturbation theory and second-order coupled-cluster singles- and-doubles model (CC2) in the electronic ground state and with CC2 in the first excited state. The CC2 method is found to be an appropriate method to calculate potential barriers in electronic excited states of such compounds.
The exact correspondence between conserved quantities of a periodic box-ball system and string solutions of the Bethe ansatz equations
Authors: Mada Jun , Idzumi Makoto , Tokihiro Tetsuji
Published: May 2006

We investigate the link between a periodic box-ball system (PBBS) and a solvable lattice model. Introducing a PBBS with an integer parameter corresponding to the dimensionality of the auxiliary space for the lattice model, we prove an important relationship between the conserved quantities of states of the PBBS and eigenvectors constructed through the string hypothesis.
A full dimensional, nine-degree-of-freedom, time-dependent quantum dynamics study for the H2+C2H reaction
Authors: Wang Dunyou
Published: May 2006

A full dimensional, nine-degree-of-freedom (9DOF), time-dependent quantum dynamics wave packet approach is presented for the study of the H2+C2H→H+C2H2 reaction system. This is the first full dimensional quantum dynamics study for a diatom-triatom reaction system. The effects of the initial vibrational and rotational excitations of the reactants on the reactivity of this reaction are investigated. This study shows that vibrational excitations of H2 enhance the reactivity; whereas, the vibrational excitations of C2H only have a small effect on the reaction probability. In addition, the bending excitations of C2H, compared to the ground state reaction probability, hinder the reactivity. Comparison of the ground state reaction probabilities of the 9DOF and 8DOF shows the reaction probability from the full dimensional calculation is larger, with more prominent resonance features.
Reactive quenching of OH(AΣ+2) by D2 studied using crossed molecular beams
Authors: Ortiz-Suárez Mariví , Witinski Mark F. , Davis H. Floyd
Published: May 2006

Reactive quenching of OH(AΣ+2,v=0) by D2 forming HOD+D was studied in crossed molecular beams. The D atom products are primarily forward scattered relative to the incident D2. The dominant mechanism involves a direct reaction from relatively large impact parameters with ∼88% of the available energy appearing in HOD internal excitation.
Free radical scavenging of xanthones from Swertia chirata Buchham and tumor cell growth inhibition
Authors: Balasundari P. , Singh S. K. , Kavimani S.
Published: May 2006

In the animal body, various electron transport chains and various enzymatic reactions either produce free radical intermediates or use free radical substrates. These free radical production have developed several mechanisms to control them. Earlier studies suggests that the Swertia chirata extract was a potent hepatoprotective drug in vivo. Since the ethanolic extract was rich in xanthones, it reduces the free radical induced lipo-peroxidation. In vivo studies on animal models have confirmed the antiradical properties of the extract. The drugs which prevent the toxic effects of free radicals are called free radical scavengers or anti oxidants. Co-enzyme Q10, Superoxide dismutase (SOD), Catalase (CAT), Glutathione peroxidase (GPX) are examples of such drugs. The lethal cell injury by CCl4 results in the elevation of lipid peroxidation products, impairment in antioxidant enzyme activities. An extraction procedure is described for the isolation of xanthones from the plant S. chirata.
The four coordinate geometric parameter: A new quantification of geometry for four coordinate aluminum and gallium
Authors: Hutchison A. R. , Mitra A. , Atwood D. A.
Published: May 2006

The chemistry of aluminum and gallium compounds has long been a major area of research. Much of this interest stems from the compound’s use as Lewis acid catalysts. Efforts to create better aluminum and gallium catalysts have often focused on the addition of new ligands to increase the Lewis acidity of the metals. However, a four coordinate Lewis acid catalyst generally must add a fifth substituent during its catalytic cycle, so the degree to which its geometry encourages this addition will also affect its activity. To help determine the degree to which a four coordinate compound is geometrically optimized to take on a fifth substituent, we have created the four coordinate geometric parameter (FGCP). The FGCP of a compound can be calculated by a simple formula utilizing the ligand-metal-ligand angles of the structure. A high FGCP value indicates a compound with an open space for a fifth substituent, while a lower FGCP value indicates a compound with a more tetrahedral geometry. A negative FGCP suggests a geometry approaching square planar, which is admittedly very unlikely for an aluminum or gallium compound. The FGCP values have been calculated for a number of structures reported in the literature, demonstrating that the method is useful for quantifying the geometry of a variety of known group thirteen compounds.
Solution behavior of Hg(II)-cystamine by Uv-Vis and 199Hg NMR
Authors: Bharara Mohan S. , Parkin Sean , Atwood David A.
Published: May 2006

The combination of HgCl2 with the disulfide salt of 2-aminoethanethiol (cystamine dihydrogen dichloride) in water yields a two-dimensional chain {[HgCl4][(NH3CH2CH2S–)2]}n (1). It consists of six-coordinate Hg in [HgCl4]n units with bridging and termainal Cl atoms. The disulfide groups, (NH3CH2CH2S–)2 are held between the [HgCl4]n chain with weak S–S interactions. The chlorides in the [HgCl4]n units are involved in intermolecular hydrogen bonding to yield a three-dimensional network. A similar reaction with the reduced form of cystamine (2-amino ethanethiol) yields a linear Hg(II)-bis-thiolate, [Hg(SCH2CH2NH3]2+ (2). When compound 1 is combined with two equivalents of NaOH it rearranges to 2 as indicated by 199Hg NMR and Uv-Vis.
Molecular association of alkyl methacrylates and alcohols in non-polar solvents: Dielectric study
Authors: Sivagurunathan P. , Dharmalingam K. , Ramachandran K. , Kalamse G. M.
Published: May 2006

Experimental results of dielectric investigations at 9.84 GHz for alkyl methacrylates (methyl methacrylate, ethyl methacrylate and butyl methacrylate) with alcohols (1-butanol, secbutanol, tert-butanol and 1-decanol) have been studied in carbon tetrachloride and benzene at 298, 303, 313 and 323 K. The relaxation time and the thermodynamical parameters, viz., free energy, enthalpy and entropy of activation have been determined using the measured dielectric data. The results show a linear dependence of relaxation time on alkyl chain length of both alcohols and alkyl methacrylates and also on the nature of the solvent. Comparative study of free energy of activation for the dielectric relaxation and viscous flow suggest the fact that the process of viscous flow involves greater interference by neighbors than does dielectric relaxation, as the latter takes place by rotation only whereas the viscous flow involves both the rotational and translational forms of motion. The thermodynamic parameter shows negative value which indicates that the reaction is forward and exothermic.
Dielectric study of methyl methacrylate-alcohol mixtures by Time Domain Reflectometry at 293K
Authors: Sivagurunathan P. , Dharmalingam K. , Ramachandran K. , Prabhakar Undre B. , Khirade P. W. , Mehrotra S. C.
Published: May 2006

Using picosecond Time Domain Reflectometry (TDR), dielectric relaxation studies have been carried out on binary mixtures of methyl methacrylate with 1-propanol, 1-butanol, 1-heptanol and 1-octanol for various concentrations over the frequency range from 10 MHz to 10 GHz at 293 K. The Kirkwood correlation factor and excess inverse relaxation times were determined and discussed to yield information on the molecular structure and dynamics of the mixture. The static permittivity and relaxation time decrease with an increase in the percentage of methyl methacrylate.
Hydrogen bonding interaction between ethyl methacrylate and alcohols in non-polar solvents: An FTIR study
Authors: Dharmalingam K. , Ramachandran K. , Sivagurunathan P.
Published: May 2006

The association between ethyl methacrylate and n-butanol, s-butanol and t-butanol in nonpolar solvents viz. n-heptane, CCl4, and benzene has been investigated by means of FTIR spectroscopy. The most likely association complex between alcohol and acrylic ester is 1:1 stoichiometric complex through the free hydroxyl group of alcohol and the carbonyl group of ester. The formation constant of the 1:1 complexes has been calculated using the Nash method. It is shown that the strength of the hydrogen bond (C=O:HO) in the various systems studied depends on the acidity of the R–OH proton and the steric factor of the alkyl group of the alkyl alcohol and also on the solvents used. The solvent effect on the formation of hydrogen bond equilibria is discussed in terms of specific interaction between the solute and solvent.
Hair as a Biological Indicator of Drug Use, Drug Abuse or Chronic Exposure to Environmental Toxicants
Authors: Boumba Vassiliki A. , Ziavrou Kallirroe S. , Vougiouklakis Theodore
Published: May 2006

In recent years hair has become a fundamental biological specimen, alternative to the usual samples blood and urine, for drug testing in the fields of forensic toxicology, clinical toxicology and clinical chemistry. Moreover, hair-testing is now extensively used in workplace testing, as well as, on legal cases, historical research etc. This article reviews methodological and practical issues related to the application of hair as a biological indicator of drug use/abuse or of chronic exposure to environmental toxicants. Hair structure and the mechanisms of drug incorporation into it are commented. The usual preparation and extraction methods as well as the analytical techniques of hair samples are presented and commented on. The outcomes of hair analysis have been reviewed for the following categories: drugs of abuse (opiates, cocaine and related, amphetamines, cannabinoids), benzodiazepines, prescribed drugs, pesticides and organic pollutants, doping agents and other drugs or substances. Finally, the specific purpose of the hair testing is discussed along with the interpretation of hair analysis results regarding the limitations of the applied procedures.
Acute Toxicity Pilot Evaluation of Proliferol in Rats and Swine
Authors: Dagenais Simon , Ogunseitan Oladele , Haldeman Scott , Wooley James R. , Zaldivar Frank , Kim Ronald C.
Published: May 2006

Proliferol is an investigational new drug containing lidocaine hydrochloride 0.25%, dextrose 12.5%, glycerin 12.5%, and phenol 1.0% in aqueous solution. Despite extensive previous experience with similar drug solutions administered in humans by intraligamentous injection for chronic musculoskeletal conditions for over 50 years, animal toxicity data are unavailable. A pilot study was conducted to assess acute toxic effects prior to undertaking further assessment of this drug. Test animals were four Sprague-Dawley rats and four Yucatan mini-swine. Rats received injections into lumbar paraspinal muscles, whereas swine received injections into lumbosacral ligaments in an attempt to mirror the method of administration in humans. Two doses were studied equivalent to 1× and 5× the typical human dose. Outcomes measured at 24 h and 14 days included clinical observations, clinical chemistry, hematology, urinalysis, local tolerance, and major organ histopathology. In rats and swine, results from clinical chemistry, hematology, and urinalysis were indicative of acute local inflammation. At the high dose, marked (rats) and moderate (swine) short-term above-normal levels in certain liver enzymes were noted. In rats and swine, local tolerance results were indicative of acute local inflammatory changes in the skin, subcutis, and muscle around the injection sites. In rats and swine, major organ histopathology results did not reveal lesions attributable to the drug and clinical observations were within normal limits. In swine, fibroplasia was noted in deeper muscle tissues after 14 days. Injections of Proliferol in lumbar paraspinal muscles in rats and lumbosacral ligaments in swine elicited a modest acute local inflammatory response with no other indications of local or systemic toxicity.
Oncogenicity Evaluations of Chemopreventive Soy Components in p53(+/–) (p53 knockout) Mice
Authors: Johnson William D. , Dooley Lawrence , Morrissey Robert L. , Arp Lawrence , Kapetanovic Izet , Crowell James A. , McCormick David L.
Published: May 2006

Epidemiologic data suggest that soy consumption may protect against cancer induction in several tissues in humans. Although the soy components responsible for this activity remain unidentified, isoflavones (e.g., genistein) and protease inhibitors (e.g., Bowman-Birk inhibitor complex [BBIC]) demonstrate chemopreventive activity in several animal cancer models. As part of their preclinical development for cancer prevention, PTI G-2535 (a soy isoflavone mixture containing 45% genistein, 23% daidzein, and 4% glycitein) and BBIC were evaluated for oncogenicity in p53(+/–) mice. In separate studies, groups of 25 p53(+/–) mice/sex received daily gavage exposure to PTI G-2535 (0, 250, 1000, or 2500 mg/kg/day) or BBIC (0, 500, 1000, or 2000 mg/kg/day) for 6 months. The high doses of both PTI G-2535 and BBIC were limited by viscosity. p-Cresidine (400 mg/kg/day) served as a positive-control article in both studies. PTI G-2535 induced no gross toxicity in any animal, but did induce a dose-related suppression of body weight gain in male mice. Modest hematologic alterations and increased liver and spleen weights were seen in both sexes exposed to the isoflavone mixture. BBIC had no significant effect on body weight, food consumption, clinical pathology, or organ weights in either sex. Histopathologic evaluations demonstrated no increases in the incidence of either benign or malignant tumors in any group of p53(+/–) mice exposed to PTI G-2535 or to BBIC. By contrast, the positive-control article, p-cresidine, induced urinary bladder cancers in both studies. Neither PTI G-2535 nor BBIC demonstrates any evidence of oncogenicity in the p53(+/–) mouse model.
Assessing Characteristics, Needs, and Preferences of a Secondary Audience for the Development of a Bilingual Parent Component to the Food Friends Social Marketing Campaign
Authors: Bellows Laura , Cole Kathleen , Anderson Jennifer
Published: May 2006

Introduction of a variety of foods to children at an early age is essential because they acquire food preferences while establishing dietary habits during the first six years of life. Food Friends— Making New Foods Fun for Kids™ is a multifaceted awareness and education program designed to encourage preschool-aged children to try new foods, and thus increase food choice and dietary variety. To further enhance this behavior, nutrition education resources are needed aimed at encouraging parents, the secondary audience, to offer new foods to their children at home. The primary objectives of this study were to determine parents' preferences and needs for information and materials to help them offer new foods and to develop a parent component to the Food Friends social marketing campaign. A needs assessment was conducted via telephone interviews with parents ( n = 26). Bilingual taglines and graphics were pretested with parents, Head Start staff, and experts ( n = 306). The end products were a bilingual tagline, a secondary message, a graphic, and educational resources targeted to low-income parents. Formative research, expert advice, and the use of the Social Learning Theory contributed to the development of each of these products. Target audience feedback was essential in the development of this theory-driven, secondary audience component of a nutrition-related social marketing campaign.
When Donor Support Ends: The Fate of Social Marketing Products and the Markets They Help Create
Authors: Agha Sohail , Do Mai , Armand Françoise
Published: May 2006

This article assesses the performance of social marketing interventions for oral contraceptives in Morocco and the Dominican Republic. These interventions were implemented under a model that has the potential to achieve sustainability; a donor-funded project partners with a manufacturer or distributor willing to market a contraceptive at a price lower than the prices of other commercial brands; the partnership makes it profitable for the commercial partner to continue the distribution and marketing of the contraceptive after donor support ceases. Multiple rounds of data from nationally representative surveys were analyzed to determine changes in the commercial sector share of oral contraceptives prior to and following the withdrawal of donor support. Particular attention was paid to changes in lower and middle income groups. In Morocco, the commercial sector share of oral contraceptives started increasing prior to the intervention and continued to do so after the withdrawal of donor support. These increases occurred for all women as well as for lower and middle income women. In the Dominican Republic, the commercial sector share of oral contraceptives increased among lower and middle income women during the period that social marketing activities were conducted and fluctuated in the period following withdrawal of donor support. The study suggests that if certain conditions are met, contraceptive social marketing interventions implemented under the manufacturer's model can contribute to a higher commercial sector share of a method among lower and middle income women and that these changes are sustainable after donor support has been withdrawn.