bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional reconstruction and synthetic mimicry of a conformational epitope using CLIPS™ technology
Authors: Timmerman Peter , Puijk Wouter C. , Meloen Rob H. 
Published: December 2007

AbstractThis paper describes immunization studies with CLIPS‐constrained peptides covering only the major part (β3‐loop) of a structurally complex antigenic site on human Follicle Stimulating Hormone β‐subunit (FSH‐β). In cases where linear and SS‐constrained peptides fail, the CLIPS‐constrained peptides generate polyclonal antibodies with high neutralizing activity for hFSH. The sera were shown to be specific for hFSH over human Luteinizing Hormone (hLH) and human Chorionic Gonadotropin (hCG). ELISA‐competition studies and circular dichroism (CD)‐measurements illustrate clearly that activity of the peptides in antibody binding and generation relates directly to precise and appropriate fixation of the peptide conformation. Design of the CLIPS‐peptides was entirely based on epitope mapping studies with two neutralizing anti‐hFSH mAbs. Both mAbs were shown to bind to a conformational epitope located at the top of the β1−β3‐loop covering the amino acid sequences Y58‐P77 (β3‐loop). The results described in this paper show that CLIPS‐constrained peptides covering the Y58‐P77 sequence provide the minimally required structural entity necessary to generate reproducibly sera with high hFSH‐neutralizing activity. Copyright © 2007 John Wiley & Sons, Ltd.magnified image
Survey of the year 2006 commercial optical biosensor literature
Authors: Rich Rebecca L. , Myszka David G. 
Published: December 2007

AbstractWe identified 1219 articles published in 2006 that described work performed using commercial optical biosensor platforms. It is interesting to witness how the biosensor market is maturing with an increased number of instrument manufacturers offering a wider variety of platforms. However, it is clear from a review of the results presented that the advances in technology are outpacing the skill level of the average biosensor user. While we can track a gradual improvement in the quality of the published work, we clearly have a long way to go before we capitalize on the full potential of biosensor technology. To illustrate what is right with the biosensor literature, we highlight the work of 10 groups who have their eye on the ball. To help out the rest of us who have the lights on but nobody home, we use the literature to address common myths about biosensor technology. Copyright © 2007 John Wiley & Sons, Ltd.
Maternal hyperthyroidism in rats impairs stress coping of adult offspring
Authors: Zhang Limei , Hernández Vito S. , Medina‐Pizarro Mauricio , Valle‐Leija Pablo , Vega‐González Arturo , Morales Teresa 
Published: December 2007

AbstractGiven the evidence that maternal hyperthyroidism (MH) compromises expression of neuronal cytoskeletal proteins in the late fetal brain by accelerated neuronal differentiation, we investigated possible consequences of MH for the emotional and cognitive functions of adult offspring during acute and subchronic stress coping. Experimental groups consisted of male rat offspring from mothers implanted with osmotic minipumps infusing either thyroxine (MH) or vehicle (Ctrl) during pregnancy. Body weight and T4 level were monitored during the first 3 postnatal months, and no differences were found with the controls. We analyzed hippocampal CA3 pyramidal neurons and dentate granular cell morphology during several postnatal stages and found increased dendritic arborization. On postnatal day 90 a modified subchronic mild stress (SCMS) protocol was applied to experimental subjects for 10 days. The Morris water maze was used before, during, and after application of the SCMS protocol to measure spatial learning. The tail suspension test (TST) and forced‐swimming test (FST) were used to evaluate behavioral despair. The MH rats displayed normal locomotor activity and spatial memory prior to SCMS, but impaired spatial learning after acute and chronic stress. In both the FST and TST we found that MH rats spent significantly more time immobile than did controls. Serum corticosterone level was found to increase after 30 min of restraint stress, and corticotropin‐releasing factor immunoreactivity was found to be increased in the central nucleus of the amygdala. Our results suggest that MH in rats leads to the offspring being more vulnerable to stress in adulthood. © 2007 Wiley‐Liss, Inc.
Changes in monthly precipitation and flood hazard in the Yangtze River Basin, China
Authors: Jiang Tong , Kundzewicz Zbigniew W. , Su Buda 
Published: December 2007

AbstractA study of change of meteorological and hydrological variables (precipitation, intense precipitation, and river flow) in the Yangtze River Basin was conducted for particular calendar months. Significant changes were found in many monthly precipitation datasets collected between 1961 and 2000. The strongest relative increase was detected in January, when the monthly precipitation is low in absolute terms. Changes in the monthly precipitation in spring and summer, from April to August, some of which are statistically significant, are of direct importance to seasonal flood hazard. The significant precipitation rise detected in June, July, and August tends to aggravate the flood hazard. Results of change detection in time series of intense precipitation in the Yangtze River Basin indicate that more precipitation falls in intense events at the expense of moderate and weak events. Significant upward trends in the discharge of the River Yangtze in summer months in the middle and lower regions were also detected. Finally, precipitation in the Yangtze River Basin and discharge in the mainstream Yangtze (gauges Yichang and Datong) in summer 1998 have been examined, in order to interpret the background of the catastrophic flood which is considered to be the costliest flood ever, worldwide. Copyright © 2007 Royal Meteorological Society
Cross‐border strategic alliances: co‐operation between firms from the United Arab Emirates and international partners
Authors: Butler Colin J. 
Published: December 2007

Abstract
The globalized business environment has accelerated the proliferation of cross‐border strategic alliances (SA). In 2007, firms in the United Arab Emirates are depending on sales in export markets more in order to make investments in industry viable in the short term and profitable in the long term.
Emirati managers of cross‐border strategic alliances need different skills and a different attitude from their predecessors in order to meet the new challenges being posed by changes in the global business environment.
Copyright © 2007 John Wiley & Sons, Ltd.
Gas‐phase pyrolytic reaction of 3‐phenoxy and 3‐phenylsulfanyl‐1‐propanol derivatives: Kinetic and mechanistic study
Authors: Dib H. H. , Ibrahim M. R. , Al‐Awadi N. A. , Ibrahim Y. A. , Al‐Awadi S. 
Published: December 2007

Abstract3‐Phenoxy‐1‐propanols 1a–c and 3‐phenylsulfanyl‐1‐propanols 2a–c containing primary, secondary, and tertiary alcohols were prepared and subjected to gas‐phase pyrolysis in a static reaction system. Pyrolysis of 4‐phenyl‐1‐butanol 3, 2‐methyl‐3‐phenyl‐1‐propanol 4, and 2‐methyl‐3‐phenylpropanoic acid 5 was also studied, and results were compared with those obtained for compounds 1–3. The pyrolytic reactions were homogeneous and followed a first‐order rate equation. Analysis of the pyrolysate showed the products to be phenol (from 1a to 1c), thiophenol (from 2a to 2c), and toluene (from 3 to 5) and carbonyl compounds. The kinetic results and product analysis of each of the nine investigated compounds are rationalized in terms of a plausible transition state for the elimination pathway. © 2007 Wiley Periodicals, Inc. 40: 51–58, 2008
Effects of unidirectional and mutual interactions between microstructures and azo dyes as “kinetic” probe molecules on cis→trans isomerization rate constants in aqueous P85 and F88 triblock copolymer solutions
Authors: Knoll Helmut 
Published: December 2007

AbstractRate constants of the thermal cis → trans isomerization of azo dyes have been studied in aqueous P85 and F88 triblock copolymer solutions by means of microsecond flash photolysis. Inflection points or maxima of the nonlinear Arrhenius plots indicate microstructure changes around the “kinetic” probe molecules. Unidirectional interactions of micelle formation on reactivity are reflected by discontinuous change of rate constants at temperatures near the critical micellization temperatures (cmT) determined by means of probe‐free methods. Mutual interactions have been identified by means of significant differences between cmT and temperatures, where rate constants change discontinuously. The type of interactions depends on the properties of probe molecules and amphiphiles. Systems as studied in this work might be models of more complex biological reaction systems with temperature‐dependent microstructure changes. © 2007 Wiley Periodicals, Inc. 40: 59–65, 2007
Rhinorrhea is increased in Parkinson's disease
Authors: Friedman Joseph H. , Amick Melissa M. 
Published: December 2007

AbstractWe have observed that rhinorrhea is increased in people with Parkinson's disease (PD) but only a single publication supports this. We performed two separate case control studies to assess the prevalence of rhinorrhea in PD in Rhode Island. One was cross‐sectional and the other in consecutive de novo patients. We further questioned subjects as to whether rhinorrhea might be associated with olfactory impairment. We found that rhinorrhea affects about half of PD patients in Rhode Island, is an early feature, being present at the time of presentation, was significantly more common than in controls and was associated with self‐perceived reduced olfaction. These observations confirm that rhinorrhea is a common problem and raise the questions as to whether some olfactory impairment found in PD could be confounded by rhinorrhea and also whether rhinorrea may be a premotor symptom. © 2007 Movement Disorder Society
A teenage boy with late onset hemophagocytic lymphohistiocytosis with predominant neurologic disease and perforin deficiency
Authors: Beaty Andrew D. , Weller Christin , Levy Beth , Vogler Carole , Ferguson William S. , Bicknese Alma , Knutsen Alan P. 
Published: December 2007

AbstractFamilial hemophagocytic lymphohistiocytosis (FHLH) is an autosomal recessive disorder of cytotoxic cell function that results in abnormal proliferation of benign lymphocytes and histiocytes in response to infectious stimuli. FHLH generally occurs in very young children, and typically presents with fever, cytopenias, coagulopathy, lymphadenopathy, and hepatosplenomegaly. Central nervous system involvement occurs frequently and may precede the development of systemic symptoms by months to years. We report a case of an 18‐year‐old male with a 2‐year history of symptoms attributed to a demyelinating disorder, who succumbed to rapidly progressive hemophagocyte lymphohistiocytosis. Post‐mortem, two distinct perforin mutations were identified. We discuss the central nervous system and genetic findings in this unusual presentation of familial hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 2008;50:1070–1072. © 2007 Wiley‐Liss, Inc.
Altered expression of genes regulating angiogenesis in experimental androgen‐independent prostate cancer
Authors: Gustavsson Heléne , Jennbacken Karin , Welén Karin , Damber Jan‐Erik 
Published: December 2007

AbstractBACKGROUNDThe aim of this study was to investigate how the expression of genes regulating angiogenesis is altered when prostate cancer cells progress into androgen‐independency.METHODSA gene array specific for angiogenesis was used to compare the human prostate cancer cell line LNCaP (androgen‐dependent) with its more angiogenic and tumorigenic subline LNCaP‐19 (androgen‐independent). Results were verified with real‐time RT‐PCR, and further investigations were focused on the angiogenesis inhibitor a disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1). Expression of ADAMTS1 was investigated in vitro as well as in subcutaneous tumors with real‐time RT‐PCR and Western blotting. Microvessel density (MVD), versican proteolysis and protein levels of TIMP‐2 and TIMP‐3, known as ADAMTS1 inhibitors, were also analyzed in tumor xenografts.RESULTSThe gene array revealed decreased expression of ADAMTS1, ephrin‐A5, fibronectin 1, and neuropilin 1 in LNCaP‐19 compared to LNCaP, while expression of midkine and VEGF were increased. Further studies showed that mRNA and protein levels of ADAMTS1 were significantly lower in LNCaP‐19 compared to LNCaP, both in vitro and in subcutaneous tumors. The amount of ADAMTS1 correlated negatively with MVD, but no relation was found between ADAMTS1 and versican proteolysis.CONCLUSIONSExpression of several genes associated with angiogenesis was altered during transition into androgen‐independency. Among these, a significant decrease was found for ADAMTS1, whose expression inversely correlated with MVD. Its role in progression of prostate cancer needs further investigation, but this inhibitor of angiogenesis could be an interesting candidate for future anti‐angiogenic therapy. Prostate 68: 161–170, 2008. © 2007 Wiley‐Liss, Inc.
A statistical rescoring scheme for protein–ligand docking: Consideration of entropic effect
Authors: Lee Juyong , Seok Chaok 
Published: December 2007

AbstractComputational prediction of protein–ligand binding modes provides useful information on the relationship between structure and activity needed for drug design. A statistical rescoring method that incorporates entropic effect is proposed to improve the accuracy of binding mode prediction. A probability function for two sampled conformations to belong to the same broad basin in the potential energy surface is introduced to estimate the contribution of the state represented by a sampled conformation to the configurational integral. The rescoring function is reduced to the colony energy introduced by Xiang et al. (Proc Natl Acad Sci USA 2002;99:7432–7437) when a particular functional form for the probability function is used. The scheme is applied to rescore protein–ligand complex conformations generated by AutoDock. It is demonstrated that this simple rescoring improves prediction accuracy substantially when tested on 163 protein–ligand complexes with known experimental structures. For example, the percentage of complexes for which predicted ligand conformations are within 1 Å root‐mean‐square deviation from the native conformations is doubled from about 20% to more than 40%. Rescoring with 11 different scoring functions including AutoDock scoring functions were also tested using the ensemble of conformations generated by Wang et al. (J Med Chem 2003;46:2287–2303). Comparison with other methods that use clustering and estimation of conformational entropy is provided. Examination of the docked poses reveals that the rescoring corrects the predictions in which ligands are tightly fit into the binding pockets and have low energies, but have too little room for conformational freedom and thus have low entropy. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Using quantum mechanics to improve estimates of amino acid side chain rotamer energies
Authors: Renfrew P. Douglas , Butterfoss Glenn L. , Kuhlman Brian 
Published: December 2007

AbstractAmino acid side chains adopt a discrete set of favorable conformations typically referred to as rotamers. The relative energies of rotamers partially determine which side chain conformations are more often observed in protein structures and accurate estimates of these energies are important for predicting protein structure and designing new proteins. Protein modelers typically calculate side chain rotamer energies by using molecular mechanics (MM) potentials or by converting rotamer probabilities from the protein database (PDB) into relative free energies. One limitation of the knowledge‐based energies is that rotamer preferences observed in the PDB can reflect internal side chain energies as well as longer‐range interactions with the rest of the protein. Here, we test an alternative approach for calculating rotamer energies. We use three different quantum mechanics (QM) methods (second order Møller‐Plesset (MP2), density functional theory (DFT) energy calculation using the B3LYP functional, and Hartree‐Fock) to calculate the energy of amino acid rotamers in a dipeptide model system, and then use these pre‐calculated values in side chain placement simulations. Energies were calculated for over 36,000 different conformations of leucine, isoleucine, and valine dipeptides with backbone torsion angles from the helical and strand regions of the Ramachandran plot. In a subset of cases these energies differ significantly from those calculated with standard molecular mechanics potentials or those derived from PDB statistics. We find that in these cases the energies from the QM methods result in more accurate placement of amino acid side chains in structure prediction tests. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Predicting protein homocysteinylation targets based on dihedral strain energy and pKa of cysteines
Authors: Sundaramoorthy Elayanambi , Maiti Souvik , Brahmachari Samir K. , Sengupta Shantanu 
Published: December 2007

AbstractA multitude of complex diseases have been linked to elevated homocysteine levels; however, till date there is no plausible explanation for a single amino acid's involvement in so many diseases. Since homocysteine is a reactive thiol amino acid and the majority of plasma homocysteine is protein thiol bound, we hypothesized that homocysteine might bind to accessible cysteine residues in target proteins, thereby modulating its structure or function or both. The parameters that dictate homocysteine–protein interaction are not well understood, and the few known homocysteine binding proteins wereidentified by a candidate protein approach. In this study, we identified potential homocysteine interacting proteins based on cysteine content, solvent accessibility of cysteine residues, and dihedral strain energies and pKa of these cysteines. Pathway mapping of the cysteine‐rich proteins revealed that proteins in the coagulation cascade, notch receptor‐mediated signaling, LDL endocytosis, programmed cell death, and extracellular matrix proteins were significantly over‐represented with cysteine‐rich proteins, and we believe that homocysteine has a high probability to bind to proteins in these pathways. In fact, several clinical studies have implicated high homocysteine levels to be associated with diseases like thrombosis, neural tube defects, and so forth, which result from dysfunction of one or more of the proteins identified in our study. Further, we successfully validated our prediction parameters on the proteins that have already been experimentally shown to bind homocysteine, and our structural analysis argues a plausible explanation for these prior reported protein interactions with homocysteine that could not be previously explained. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Binding of sulfonium‐ion analogues of di‐epi‐swainsonine and 8‐epi‐lentiginosine to Drosophila Golgi α‐mannosidase II: The role of water in inhibitor binding
Authors: Kumar Nag S. , Kuntz Douglas A. , Wen Xin , Pinto B. Mario , Rose David R. 
Published: December 2007

AbstractRetaining glycosidases operate by a two‐step catalytic mechanism in which the transition states are characterized by buildup of a partial positive charge at the anomeric center. Sulfonium‐ion analogues of the naturally occurring glycosidase inhibitors, swainsonine and 8‐epi‐lentiginosine, in which the bridgehead nitrogen atom is replaced by a sulfonium‐ion, were synthesized in order to test the hypothesis that a sulfonium salt carrying a permanent positive charge would be an effective glycosidase inhibitor. Initial prediction based on computational docking indicated three plausible binding modes to Drosophila Golgi α‐mannosidase II (dGMII), the most likely being close to that of swainsonine. Observation of the binding of di‐epi‐thioswainsonine and 8‐epi‐thiolentiginosine to dGMII from crystallographic data, however, revealed an orientation different from swainsonine in the active site. Screening these two compounds against dGMII shows that they are inhibitors with IC50 values of 2.0 and 0.014 mM, respectively. This dramatic difference in affinity between the two compounds, which differ by only one hydroxyl group, is rationalized in terms of bound water molecules and the water molecule substructure in the active site, as identified by comparison of high resolution X‐ray crystal structures of several dGMII‐inhibitor complexes. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Exploring the protein G helix free‐energy surface by solute tempering metadynamics
Authors: Camilloni Carlo , Provasi Davide , Tiana Guido , Broglia Ricardo A. 
Published: December 2007

AbstractThe free‐energy landscape of the α‐helix of protein G is studied by means of metadynamics coupled with a solute tempering algorithm. Metadynamics allows to overcome large energy barriers, whereas solute tempering improves the sampling with an affordable computational effort. From the sampled free‐energy surface we are able to reproduce a number of experimental observations, such as the fact that the lowest minimum corresponds to a globular conformation displaying some degree of β‐structure, that the helical state is metastable and involves only 65% of the chain. The calculations also show that the system populates consistently a π‐helix state and that the hydrophobic staple motif is present only in the free‐energy minimum associated with the helices, and contributes to their stabilization. The use of metadynamics coupled with solute tempering results then particularly suitable to provide the thermodynamics of a short peptide, and its computational efficiency is promising to deal with larger proteins. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Huntingtin interacting protein HYPK is intrinsically unstructured
Authors: Raychaudhuri Swasti , Majumder Pritha , Sarkar Somosree , Giri Kalyan , Mukhopadhyay Debashis , Bhattacharyya Nitai P. 
Published: December 2007

AbstractTo characterize HYPK, originally identified as a novel huntingtin (Htt) interacting partner by yeast two hybrid assay, we used various biophysical and biochemical techniques. The molecular weight of the protein, determined by gel electrophoresis, was found to be about 1.3‐folds (∼22 kDa) higher than that obtained from mass spectrometric analysis (16.9 kDa). In size exclusion chromatography experiment, HYPK was eluted in three fractions, the hydrodynamic radii for which were calculated to be ∼1.5‐folds (23.06 Å) higher than that expected for globular proteins of equivalent mass (17.3 Å). The protein exhibited predominantly (63%) random coil characteristics in circular dichroism spectroscopy and was highly sensitive to limited proteolysis by trypsin and papain, indicating absence of any specific domain. Experimental evidences with theoretical analyses of amino acids composition of HYPK and comparison with available published data predicts that HYPK is an intrinsically unstructured protein (IUP) with premolten globule like conformation. In presence of increasing concentration of Ca2+, HYPK showed conformational alterations as well as concomitant reduction of hydrodynamic radius. Even though any link between the natively unfolded nature of HYPK, its conformational sensitivity towards Ca2+ and interaction with Htt is yet to be established, its possible involvement in Huntington's disease pathogenesis is discussed. Proteins 2008. © 2007 Wiley‐Liss, Inc.