bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Impromidine‐ and Arpromidine‐Derived Guanidines on Recombinant Human and Guinea Pig Histamine H1and H2Receptors
Authors: Xie Sheng‐Xue , Schalkhausser Fabian , Ye Qi‐Zhuang , Seifert Roland , Buschauer Armin 
Published: January 2007

AbstractImidazolylpropylguanidines derived from impromidine and arpromidine are more potent and efficacious agonists at the guinea pig histamine H2receptor (gpH2R) than at the human H2R (hH2R) in the GTPase assay. Additionally, such guanidines are histamine H1receptor (H1R) antagonists with preference for the human relative to the guinea pig receptor. The purpose of this study was to examine structure‐activity relationships of guanidines at human and guinea pig H1R and H2R species isoforms expressed in Sf9 insect cells. Three impromidine analogues and six arpromidine analogues exhibited agonistic activity at H2R and antagonistic activity at H1R as assessed in the steady‐state GTPase assay. Species selectivity of derivatives was similar as compared with the parent compounds. None of the structural modifications examined (different aromatic ring systems and different ring substituents) was superior in terms of H2R potency and efficacy relative to impromidine and arpromidine, respectively. These data point to substantial structural constraints at the agonist binding site of H2R. Guanidines exhibited distinct structure‐activity relationships for H1R antagonism in a radioligand competition binding assay and the GTPase assay and for H1R inverse agonism. Our data indicate that it is difficult to obtain guanidine‐type agonists with high potency and high efficacy for hH2R, but those compounds may be useful tools for exploring the antagonist binding site and constitutive activity of H1R.
Activity based fingerprinting of proteases using FRET peptides
Authors: Sun Hongyan , Panicker Resmi C. , Yao Shao Q. 
Published: January 2007

AbstractWe have successfully developed a protease assay using fluorescence resonance energy transfer based peptide libraries, which allows not only general detection of enzymatic activities, but more importantly substrate fingerprinting of proteases from different classes. The method allows the generation of substrate fingerprints of a protease from both the nonprime and prime sites. Therefore, it is well suited for profiling of major metalloproteases such as thermolysin and MMPs. We envisage that this method will provide a useful tool in the emerging field of “Catalomics” for high‐throughput studies of proteases. © 2007 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 88: 141–149, 2007.This article was originally published online as an accepted preprint. The ‘Published Online’ date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
From the test tube to the cell: Exploring the folding and aggregation of a β‐clam protein
Authors: Ignatova Zoya , Krishnan Beena , Bombardier Jeffrey P. , Marcelino Anna Marie C. , Hong Jiang , Gierasch Lila M. 
Published: January 2007

AbstractA crucial challenge in present biomedical research is the elucidation of how fundamental processes like protein folding and aggregation occur in the complex environment of the cell. Many new physico‐chemical factors like crowding and confinement must be considered, and immense technical hurdles must be overcome in order to explore these processes in vivo. Understanding protein misfolding and aggregation diseases and developing therapeutic strategies to these diseases demand that we gain mechanistic insight into behaviors and misbehaviors of proteins as they fold in vivo. We have developed a fluorescence approach using FlAsH labeling to study the thermodynamics of folding of a model β‐rich protein, cellular retinoic acid binding protein (CRABP) in Escherichia coli cells. The labeling approach has also enabled us to follow aggregation of a modified version of CRABP and chimeras between CRABP and huntingtin exon 1 with its glutamine repeat tract. In this article, we review our recent results using FlAsH labeling to study in‐vivo folding and present new observations that hint at fundamental differences between the thermodynamics and kinetics of protein folding in vivo and in vitro. © 2007 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 88: 157–163, 2007.This article was originally published online as an accepted preprint. The ‘Published Online’ date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
NMR analysis of G7‐18NATE, a nonphosphorylated cyclic peptide inhibitor of the Grb7 adapter protein
Authors: Porter C. J. , Wilce J. A. 
Published: January 2007

AbstractG7‐18NATE is a nonphosphorylated, cyclic peptide that specifically inhibits the Grb7 adapter protein implicated in several pathways critical to cell proliferation and migration. It has been shown that G7‐18NATE is able to compete with natural ligands for the Grb7 SH2 phosphotyrosine binding site, and to attenuate cell migration in a pancreatic cancer cell line. It is thus an important lead in the development of a selective inhibitor of Grb7 and potential novel anticancer therapeutics. The current study reports the solution properties of G7‐ 18NATE determined using NMR spectroscopy, in both water (pH 2–3) and phosphate buffer (pH 6.0), with 100 mM NaCl. The spectra reveal that G7‐18NATE exists in two distinguishable conformational states on the NMR timescale, most likely due to cis‐trans proline isomerization. In addition, the chemical shift data are consistent with a tendency of G7‐18NATE to form a turn about the YDN motif, known to be important for binding, and suggest that this turn is stabilized in low salt and low pH conditions. Low NH temperature coefficients of Tyr‐5 and Asn‐7 amide protons may reflect their involvement in the formation of hydrogen bonds that stabilize such a turn. Overall, however, the peptide does not form a rigid structure, but exists in a highly flexible state in solution. Averaged 3JNH‐αH coupling constants and a lack of interresidue NOEs are characteristic of such peptide solution behavior. This suggests that there is scope for increasing the rigidity of the peptide that may enhance its binding affinity and specificity for Grb7. © 2007 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 88: 174–181, 2007.This article was originally published online as an accepted preprint. The ‘Published Online’ date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Peptides as transmembrane segments: Decrypting the determinants for helix–helix interactions in membrane proteins
Authors: Rath Arianna , Johnson Rachel M. , Deber Charles M. 
Published: January 2007

AbstractAlthough the structural analysis of membrane proteins is advancing, an understanding of the basic principles that underlie their folding and assembly remains limited because of the high insolubility intrinsic to these molecules and concomitant challenges in obtaining crystals. Fortunately, from an experimental standpoint, membrane protein folding can be approximated as the rigid‐body docking of pre‐formed α‐helical transmembrane segments one with another to form the final functional protein structure. Peptides derived from the sequences of native α‐helical transmembrane segments and those that mimic their properties are therefore valuable in the experimental evaluation of protein folding within the membrane. Here we present an overview of the progress made in our laboratory and elsewhere in using peptide models toward defining the sequence requirements and forces stabilizing membrane protein folds. © 2007 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 88: 217–232, 2007.This article was originally published online as an accepted preprint. The ‘Published Online’ date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Upregulation of aggrecan, link protein 1, and hyaluronan synthases during formation of perineuronal nets in the rat cerebellum
Authors: Carulli Daniela , Rhodes Kate E. , Fawcett James W. 
Published: January 2007

AbstractExtracellular matrix molecules accumulate around central nervous system neurons during postnatal development, forming so‐called perineuronal nets (PNNs). PNNs play a role in restricting plasticity at the end of critical periods. In the adult rat cerebellum, PNNs are found around large, deep cerebellar nuclei (DCN) neurons and Golgi neurons and are composed of chondroitin sulfate proteoglycans (CSPGs), tenascin‐R (TN‐R), hyaluronan (HA), and link proteins, such as cartilage link protein 1 (Crtl1). Granule cells and Purkinje cells are surrounded by a partially organized matrix. Both glial cells and neurons surrounded by PNNs are the site of synthesis of some CSPGs and of TN‐R, but only neurons produce HA synthetic enzymes (HASs), thus HA, and link proteins, which are scaffolding molecules for an organized matrix. To elucidate the mechanisms of formation of PNNs, we analyzed by immunohistochemistry and in situ hybridization which PNN components are upregulated during PNN formation in rat cerebellar postnatal development and what cell types express them. We observed that Wisteria floribunda agglutinin‐binding PNNs develop around DCN neurons from postnatal day (P)7 and around Golgi neurons from P14. At the same time as their PNNs start to form, these neurons upregulate aggrecan, Crtl1, and HASs mRNAs. However, Crtl1 is the only PNN component to be expressed exclusively in neurons surrounded by PNNs. The other link protein that shows a perineuronal net pattern in the DCN, Bral2, is upregulated later during development. These data suggest that aggrecan, HA, and, particularly, Crtl1 might be crucial elements for the initial assembly of PNNs. J. Comp. Neurol. 501:83–94, 2007. © 2007 Wiley‐Liss, Inc.
Flow cytometry PRA using lymphocyte pools from random donors
Authors: Won Dong Il , Jung Hee Du , Jung Ok‐Ju , Huh Seung , Suh Jang Soo 
Published: January 2007

AbstractBackground:Pools of lymphocytes from carefully chosen donors have been used for flow cytometry (FC) panel reactive antibody (PRA) assays. We intended to devise an FC PRA assay using mixed lymphocyte pools from a large number of randomly selected donors (RD FC PRA) to accurately predict the likelihood of a positive HLA crossmatch.Methods:Lymphocyte pools were prepared from randomly selected donors (N= 120). %PRA was calculated based on the anti‐IgG FITC histogram of the T cells. The proposed RD FC PRA assay was assessed in comparison with the bead FC PRA, antiglobulin‐augmented CDC (AHG‐CDC) PRA assay, and the expected %PRA calculated by summing up the antigen frequencies of the known specificities.Results:In 29 FC crossmatch positive sera, the positivity rate for the bead FC, RD FC, and AHG‐CDC PRA was 100, 100, and 79%, and the mean %PRA was 77% ± 0.205). In 19 sensitized patients with a negative FC crossmatch, the positivity rate was 21% using the RD FC PRA and 16% using the bead FC PRA, which suggested that both assays had similar abilities to detect low levels of HLA antibodies.Conclusions:The RD FC PRA assay allows easy panel preparation, reduces cost, and naturally reflects the probabilities of a positive crossmatch in the population to which the cadaveric donor belongs. Therefore, this new assay is expected to be useful as another approach to determine the % PRA. © 2007 Clinical Cytometry Society
Relationship between blood compatibility and water structure—Comparative study between 2‐methoxyethylacrylate‐ and 2‐methoxyethylmethacrylate‐based random copolymers
Authors: Hirota Etsuko , Tanaka Masaru , Mochizuki Akira 
Published: January 2007

AbstractWe have proposed that the excellent blood compatibility of poly(2‐methoxyethylacrylate (MEA)) is caused by freezing bound water contained in it on the basis of results on platelet activation (Tanaka and Mochizuki, J Biomed Mater Res A 2004; 68:684–695). To clarify the applicability of this mechanism to other indexes for blood compatibility, the relationship between complement activation and water structure was investigated by using two copolymers, poly(MEA‐2‐hydroxyethylmethacrylate (HEMA)) and poly(2‐methoxyethylmethacrylate (MEMA)‐HEMA), where HEMA content was varied from 25 to 90 mol %. ESCA analysis revealed that the surface compositions of these copolymers (dry state) agreed with the compositions determined by 1H NMR. However, analysis by water contact angle (wet state) showed that their surfaces were quite different. The contact angle of poly(MEMA‐HEMA) depended on the monomer composition, whereas the angle of poly(MEA‐HEMA) was close to that of polyHEMA regardless of the monomer composition. The effect of HEMA content in the copolymers on complement activation (production of C3a) was investigated in an in vitro test. The activation by poly(MEMA‐HEMA) was enhanced according to the HEMA content, while the activation by poly(MEA‐HEMA) with 0–40 mol % of HEMA was weak and did not depend on the HEMA content. These properties are discussed from the viewpoints of the water structure observed by DSC and the surface structure. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007.
Studies on the importance of sympathetic innervation, adrenergic receptors, and a possible local catecholamine production in the development of patellar tendinopathy (tendinosis) in man
Authors: Danielson Patrik , Alfredson Håkan , Forsgren Sture 
Published: January 2007

AbstractChanges in the patterns of production and in the effects of signal substances may be involved in the development of tendinosis, a chronic condition of pain in human tendons. There is no previous information concerning the patterns of sympathetic innervation in the human patellar tendon. In this study, biopsies of normal and tendinosis patellar tendons were investigated with immunohistochemical methods, including the use of antibodies against tyrosine hydroxylase (TH) and neuropeptide Y, and against α1‐, α2A‐, and β1‐adrenoreceptors. It was noticed that most of the sympathetic innervation was detected in the walls of the blood vessels entering the tendon through the paratendinous tissue, and that the tendon tissue proper of the normal and tendinosis tendons was very scarcely innervated. Immunoreactions for adrenergic receptors were noticed in nerve fascicles containing both sensory and sympathetic nerve fibers. High levels of these receptors were also detected in the blood vessel walls; α1‐adrenoreceptor immunoreactions being clearly more pronounced in the tendinosis tendons than in the tendons of controls. Interestingly, immunoreactions for adrenergic receptors and TH were noted for the tendon cells (tenocytes), especially in tendinosis tendons. The findings give a morphological correlate for the occurrence of sympathetically mediated effects in the patellar tendon and autocrine/paracrine catecholamine mechanisms for the tenocytes, particularly, in tendinosis. The observation of adrenergic receptors on tenocytes is interesting, as stimulation of these receptors can lead to cell proliferation, degeneration, and apoptosis, events which are all known to occur in tendinosis. Furthermore, the results imply that a possible source of catecholamine production might be the tenocytes themselves. Microsc. Res. Tech., 2007. © 2007 Wiley‐Liss, Inc.
Comprehensive analysis of proteins of pH fractionated samples using monolithic LC/MS/MS, intact MW measurement and MALDI‐QIT‐TOF MS
Authors: Yoo Chul , Patwa Tasneem H. , Kreunin Paweena , Miller Fred R. , Huber Christian G. , Nesvizhskii Alexey I. , Lubman David M. 
Published: January 2007

AbstractA comprehensive platform that integrates information from the protein and peptide levels by combining various MS techniques has been employed for the analysis of proteins in fully malignant human breast cancer cells. The cell lysates were subjected to chromatofocusing fractionation, followed by tryptic digestion of pH fractions for on‐line monolithic RP‐HPLC interfaced with linear ion trap MS analysis for rapid protein identification. This unique approach of direct analysis of pH fractions resulted in the identification of large numbers of proteins from several selected pH fractions, in which approximately 1.5 µg of each of the pH fraction digests was consumed for an analysis time of ca 50 min. In order to combine valuable information retained at the protein level with the protein identifications obtained from the peptide level information, the same pH fraction was analyzed using nonporous (NPS)‐RP‐HPLC/ESI‐TOF MS to obtain intact protein MW measurements. In order to further validate the protein identification procedures from the fraction digest analysis, NPS‐RP‐HPLC separation was performed for off‐line protein collection to closely examine each protein using MALDI‐TOF MS and MALDI‐quadrupole ion trap (QIT)‐TOF MS, and excellent agreement of protein identifications was consistently observed. It was also observed that the comparison to intact MW and other MS information was particularly useful for analyzing proteins whose identifications were suggested by one sequenced peptide from fraction digest analysis. Copyright © 2007 John Wiley & Sons, Ltd.
In healthy subjects without knee osteoarthritis, the peak knee adduction moment influences the acute effect of shoe interventions designed to reduce medial compartment knee load
Authors: Fisher David S. , Dyrby Chris O. , Mündermann Annegret , Morag Erez , Andriacchi Thomas P. 
Published: January 2007

AbstractThe purpose of this study was to evaluate shoe sole material stiffness changes and angle changes that are intended to reduce the peak knee adduction moment during walking. Fourteen physically active adults were tested wearing their personal shoes (control) and five intervention pairs, two with stiffness variations, two with angle variations, and a placebo shoe. The intervention shoes were evaluated based on how much they reduced the peak knee adduction moment compared to the control shoe. An ANOVA test was used to detect differences between interventions. Linear regression analysis was used to determine a relationship between the magnitude of the knee adduction moment prior to intervention and the effectiveness of the intervention in reducing the peak knee adduction moment. Peak knee adduction moments were reduced for the altered stiffness and altered angle shoes (p < 0.010), but not for the placebo shoe (p = 0.363). Additionally, linear regression analysis showed that subjects with higher knee adduction moments prior to intervention had larger reductions in the peak knee adduction moment (p < 0.010). These results demonstrate that shoe sole stiffness and angle interventions can be used to reduce the peak knee adduction moment and that subjects with initially higher peak knee adduction moments have higher reductions in their peak knee adduction moments. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:540–546, 2007
Variational transition‐state theory study of the atmospheric reaction OH + O3 → HO2 + O2
Authors: Ju Li‐Ping , Han Ke‐Li , Varandas António J. C. 
Published: January 2007

AbstractWe report variational transition‐state theory calculations for the OH + O3→ HO2 + O2 reaction based on the recently reported double many‐body expansion potential energy surface for ground‐state HO4 [Chem Phys Lett 2000, 331, 474]. The barrier height of 1.884 kcal mol−1 is comparable to the value of 1.77–2.0 kcal mol−1 suggested by experimental measurements, both much smaller than the value of 2.16–5.11 kcal mol−1 predicted by previous ab initio calculations. The calculated rate constant shows good agreement with available experimental results and a previous theoretical dynamics prediction, thus implying that the previous ab initio calculations will significantly underestimate the rate constant. Variational and tunneling effects are found to be negligible over the temperature range 100–2000 K. The O1O2 bond is shown to be spectator like during the reactive process, which confirms a previous theoretical dynamics prediction. © 2007 Wiley Periodicals, Inc. 39: 148–153, 2007
Sources of axonal calcium loading during in vitro ischemia of rat dorsal roots
Authors: Petrescu Nicolae , Micu Ileana , Malek Sameh , Ouardouz Mohamed , Stys Peter K. 
Published: January 2007

AbstractA detailed understanding of injury mechanisms in peripheral nerve fibers will help guide successful design of therapies for peripheral neuropathies. This study was therefore undertaken to examine the ionic mechanisms of Ca2+overload in peripheral myelinated fibers subjected to chemical inhibition of energy metabolism. Myelinated axons from rat dorsal roots were co‐loaded with Ca2+‐sensitive (Oregon Green BAPTA‐1) and Ca2+‐insensitive (Alexa Fluor 594) dextran‐conjugated fluorophores and imaged using confocal laser scanning microscopy. Axoplasmic regions were clearly outlined by the Ca2+‐insensitive dye, from which axonal Ca2+‐dependent fluorescence changes (FCa.ax) were measured. Block of Na+–K+ATPase (ouabain), opening of Na+channels (veratridine), and inhibiting energy metabolism (iodoacetate + NaN3) caused a rapid rise inFCa.axto 96% above control after 30 min. Chemical ischemia (iodoacetate + NaN3) caused a more gradual increase inFCa.ax(54%), which was almost completely dependent on bath Ca2+, indicating that most of the Ca2+accumulation occurred via influx across the axolemma. Na+channel block (tetrodotoxin) reduced ischemicFCa.axrise (14%); however, inhibition of L‐type Ca2+channels (nimodipine) had no effect (60%). In contrast, Na+–Ca2+exchange inhibition (KB‐R7943) significantly reduced ischemicFCa.axrise (18%). Together our results indicate that the bulk of Ca2+overload in injured peripheral myelinated axons occurs via reverse Na+–Ca2+exchange, driven by axonal Na+accumulation through voltage‐gated tetrodotoxin‐sensitive Na+channels. This mechanism may represent a viable therapeutic target for peripheral neuropathies. Muscle Nerve, 2007
Integration of structure and control using an evolutionary approach: an application to the optimal concurrent design of a CVT
Authors: Portilla‐Flores Edgar A. , Mezura‐Montes Efrén , Álvarez‐Gallegos Jaime , Coello‐Coello Carlos A. , Cruz‐Villar Carlos A. 
Published: January 2007

AbstractIn this paper, a concurrent design methodology to formulate the mechatronic design problem is presented. The methodology proposes to state the mechatronic design problem as a dynamic optimization problem. In order to explain the methodology, the concurrent design of pinion–rack continuously variable transmission (CVT) is carried out. Two optimization techniques, one based on a mathematical programming method and the other based on a novel evolutionary approach, are used to solve it. The behaviour of both approaches is compared, based on quality and the computational time required by each of them in a common platform. Copyright © 2007 John Wiley & Sons, Ltd.