bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microanatomy and surgical relevance of the olfactory cistern
Authors: Wang Shou‐Sen , Zheng He‐Ping , Zhang Xiang , Zhang Fa‐Hui , Jing Jun‐Jie , Wang Ru‐Mi 
Published: December 2007

AbstractAll surgical approaches to the anterior skull base involve the olfactory cistern and have the risk of damaging the olfactory nerve. The purpose of this study was to describe the microanatomical features of the olfactory cistern and discuss its surgical relevance. In this study, the olfactory cisterns of 15 formalin‐fixed adult cadaveric heads were dissected using a surgical microscope. The results showed that the olfactory cistern was situated in the superficial part of the olfactory sulcus, which separated the gyrus retus from the orbital gyrus. In coronal section, the cistern was triangular in shape; its anterior part enveloped the olfactory bulbs and was high and broad; its posterior part was medial‐superior to internal carotid artery and was also much broader. There were one or several openings in the inferior wall of the posterior part in 53.4% of the cisterns. The olfactory cistern communicated with the surrounding subarachnoind cisterns through these openings. The middle part of the olfactory cistern gradually narrowed down posteriorly. Most cisterns were spacious with a few fibrous trabeculas and bands between the olfactory nerves and cistern walls. However 23% of the cisterns were narrow with the cistern walls tightly encasing the olfactory nerve. There were two or three of arterial loops in each olfactory sulcus, from which long, fine olfactory arteries originated. The olfactory arteries coursed along the olfactory nerve and gave off many terminal branches to provide the main blood supply to the olfactory nerve in most cisterns, but the blood supply was in segmental style in a few cisterns. Moreover, the veins of the cistern appeared to be more segmental than the olfactory arteries in most cisterns. These results suggested that most olfactory cisterns are spacious with relatively independent blood supply, and it is reasonable to separate the olfactory tract with its independent blood supply from the frontal lobe by 1–2 cm in the subfrontal approach, the pterional approach, or anterior interhemispheric approach. However, in the minority of cases, separation of the olfactory tract is not safe because of the anterior origin of the olfactory arteries or segmental blood supply. It is difficult to separate the olfactory nerve without any damage to the olfactory nerve, even with very skilled hands. © 2007 Wiley‐Liss, Inc. Microsurgery, 2008.
Obtaining smooth mesh transitions using vertex optimization
Authors: Brewer M. 
Published: December 2007

AbstractMesh optimization has proven to be an effective way to improve mesh quality for arbitrary Lagrangian Eulerian (ALE) simulations. To date, however, most of the focus has been on improving the geometric shape of individual elements, and these methods often do not result in smooth transitions in element size or aspect ratio across groups of elements. We present an extension to the mean ratio optimization that addresses this problem and yields smooth transitions within regions and across regions in the ALE simulation. While this method is presented in the context of ALE simulations, it is applicable to a wider set of applications that require mesh improvement, including the mesh generation process. Published in 2007 by John Wiley & Sons, Ltd.
Patient groups
Authors: Knight Alison 
Published: December 2007

AbstractEpilepsy Action is the largest member‐led epilepsy organisation in the UK.The charitable association was founded in 1950 to improve the lives of people with epilepsy.As a campaigning charity,EpilepsyAction regularly speaks out on behalf of people with epilepsy on issues such as consistency of supply of medication,better health care,and a wider understanding of epilepsy among teachers, employers and the Government. Here, Alison Knight outlines the main aims and some of the current work of the organisation. Copyright © 2007 Wiley Interface Ltd
Dyspnea experience and management strategies in patients with lung cancer
Authors: Henoch Ingela , Bergman Bengt , Danielson Ella 
Published: December 2007

AbstractObjective: The aim of this paper was to describe lung cancer patients' experience of dyspnea and their strategies for managing the dyspnea.Methods: Semi‐structured interviews with two main questions about dyspnea experiences and management were conducted with 20 patients with lung cancer, not amenable to curative treatment, who had completed life prolonging treatments. Data analysis was made with a descriptive, qualitative content analysis.Results: The two questions resulted in two domains with 7 categories and subcategories. The experience of dyspnea included four categories: ‘Triggering factors’ included circumstances contributing to dyspnea, which comprised physical, psychosocial and environmental triggers. Bodily manifestations were considered to be the core of the experience. ‘Immediate reactions’ concerned physical and psychological impact. The long‐term reactions included limitations, increased dependence and existential impact concerning hope, hopelessness and thoughts of death. The experience of managing dyspnea included three categories: ‘Bodily strategies’, ‘psychological strategies’ and ‘medical strategies’.Conclusion: Dyspnea experience is a complex experience which influences the life of the patients both with immediate reactions and long‐term reactions concerning physical, emotional and existential issues in life and patients address this experience with managing strategies in order to take control of their situation, although they do not seem to be able to meet the existential distress they experience. Copyright © 2007 John Wiley & Sons, Ltd.
The association of prostate stem cell antigen (PSCA) mRNA expression and subsequent prostate cancer risk in men with benign prostatic hyperplasia following transurethral resection of the prostate
Authors: Zhigang Zhao , Wenlu Shen 
Published: December 2007

AbstractBACKGROUNDPrior data showed prostate stem cell antigen (PSCA) mRNA expression in benign prostatic hyperplasia (BPH) tissues. The purpose of the present investigation was to determine whether PSCA mRNA expression in resected BPH samples was associated with the subsequent presence of cancer following transurethral resection of the prostate (TURP).METHODSPSCA in situ hybridization was performed on the TURP‐resected tissues from 288 patients, who were histopathologically confirmed BPH without cancer. All these patients were continuously followed for 9–70 months postoperatively. Univariate and multivariate cox regression analyses were used to evaluate the predictive performance of PSCA mRNA for subsequent cancer onset following TURP.RESULTSPSCA mRNA was detected in 93/288 (32.3%) of the resected BPH specimens, with a mean positive‐labeling cells of 23.8%, in which 22 patients (23.7%) were identified as having PCa on follow‐up. Of 195 patients with negative expression for PSCA mRNA 2 (1.0%) were subsequently found with PCa. PSCA mRNA expression levels were directly proportional to higher Gleason score and clinical T stage. Univariate and multivariate cox regression analyses demonstrated that only PSCA mRNA expression was predictive of the subsequent cancer development after TURP, however, PSA velocity was an univariately significant but not multivariately significant predictor.CONCLUSIONSThis prospective study identifies PSCA mRNA in BPH as a significant predictor of cancer development after TURP, suggesting that PSCA may be used to identify patients who are at high risk for subsequent cancer onset following TURP for BPH and the PSCA test may be useful when applied for repeat biopsies. Prostate 68: 190–199, 2008. © 2007 Wiley‐Liss, Inc.
Proteasome inhibition blocks caspase‐8 degradation and sensitizes prostate cancer cells to death receptor‐mediated apoptosis
Authors: Thorpe Jeffery A. , Christian Perry A. , Schwarze Steven R. 
Published: December 2007

AbstractBACKGROUNDProteasome inhibition through the administration of Velcade is a viable chemotherapeutic strategy that is approved to treat multiple myeloma and is being evaluated for efficacy against prostate cancer. Currently, the apoptotic pathways that contribute to this anticancer response are poorly understood. Our goal is to test the extent to which proteasome inhibition modulates apoptosis through death receptor pathways.METHODSSeveral prostate cancer cell lines and primary prostate epithelial cells (PrECs) were used as models. The death receptor pathway was activated by the expression of Fas ligand (FasL) or addition of TNF‐related apoptosis‐inducing ligand (TRAIL) in the presence or absence of proteasome inhibitors. The apoptotic response was quantified by annexin V, TUNEL and nuclear condensation assays. Western blot analysis was conducted to quantify protein levels and enzyme assays were used to measure caspase activity.RESULTSProteasome inhibition markedly sensitized prostate cancer cells to apoptosis initiated by Fas ligand (FasL) or TRAIL. In the presence of either death ligand, procaspase‐8 processing occurred, but led to minimal amounts of active caspase‐8. The addition of Velcade, however, led to robust active caspase‐8 protein abundance and activity. In the presence of Velcade the caspase‐8 p18 subunit half‐life increased from 22 min to over 2 hr.CONCLUSIONSThese findings demonstrate that proteasome inhibition can sensitize cells to apoptosis elicited by tumor necrosis factor ligands and retarding caspase‐8 degradation provides one explanation for this activity. This study suggests that the clinical efficacy of Velcade may result, at least in part, from the activity of death ligands. Prostate 68: 200–209, 2008. © 2007 Wiley‐Liss, Inc.
Remote homology detection of integral membrane proteins using conserved sequence features
Authors: Bernsel Andreas , Viklund Håkan , Elofsson Arne 
Published: December 2007

AbstractCompared with globular proteins, transmembrane proteins are surrounded by a more intricate environment and, consequently, amino acid composition varies between the different compartments. Existing algorithms for homology detection are generally developed with globular proteins in mind and may not be optimal to detect distant homology between transmembrane proteins. Here, we introduce a new profile–profile based alignment method for remote homology detection of transmembrane proteins in a hidden Markov model framework that takes advantage of the sequence constraints placed by the hydrophobic interior of the membrane. We expect that, for distant membrane protein homologs, even if the sequences have diverged too far to be recognized, the hydrophobicity pattern and the transmembrane topology are better conserved. By using this information in parallel with sequence information, we show that both sensitivity and specificity can be substantially improved for remote homology detection in two independent test sets. In addition, we show that alignment quality can be improved for the most distant homologs in a public dataset of membrane protein structures. Applying the method to the Pfam domain database, we are able to suggest new putative evolutionary relationships for a few relatively uncharacterized protein domain families, of which several are confirmed by other methods. The method is called Searcher for Homology Relationships of Integral Membrane Proteins (SHRIMP) and is available for download at http://www.sbc.su.se/shrimp/. Proteins 2008. © 2007 Wiley‐Liss, Inc.
The investigation of interactions of κ‐Hefutoxin1 with the voltage‐gated potassium channels: A computational simulation
Authors: Zarrabi M. , Naderi‐Manesh H. 
Published: December 2007

Abstractκ‐Hefutoxin1 is a K+ channel‐blocking toxin from the scorpion Heterometrus fluvipes. It is a 22‐residue protein that adapts a novel fold of two parallel helices linked by two disulfide bridges without β‐sheets. Recognition of interactions of κ‐Hefutoxin1 with the voltage‐gated potassium channels, Kv1.1, Kv1.2, and Kv1.3, was studied by 3D‐Dock software package. All structures of κ‐Hefutoxin1 were considered during the simulations, which indicated that even small changes in the structure of κ‐Hefutoxin1 considerably affected both the recognition and the binding between κ‐Hefutoxin1 and the Kv1 channels. κ‐Hefutoxin1 is located around the extracellular part of the Kv1 channels, making contacts with its helices. Lys 19, Tyr 5, Arg 6, Trp 9, or Arg 10 in the toxin and residues Asp 402, His 404, Thr 407,Gly 401, and Asp 386 in each subunit of the Kv potassium channel are the key residues for the toxin‐channel recognition. Moreover, the simulation result demonstrates that the hydrophobic interactions are important in interaction of negatively charged toxins with potassium channels. The results of our docking/molecular dynamics simulations indicate that our 3D model structure of the κ‐Hefutoxin1‐complex is both reasonable and acceptable and could be helpful for smarter drug design and the blocking agents of Kv1 channels. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Probing electrostatic interactions and ligand binding in aspartyl‐tRNA synthetase through site‐directed mutagenesis and computer simulations
Authors: Thompson Damien , Lazennec Christine , Plateau Pierre , Simonson Thomas 
Published: December 2007

AbstractFaithful genetic code translation requires that each aminoacyl‐tRNA synthetase recognise its cognate amino acid ligand specifically. Aspartyl‐tRNA synthetase (AspRS) distinguishes between its negatively‐charged Asp substrate and two competitors, neutral Asn and di‐negative succinate, using a complex network of electrostatic interactions. Here, we used molecular dynamics simulations and site‐directed mutagenesis experiments to probe these interactions further. We attempt to decrease the Asp/Asn binding free energy difference via single, double and triple mutations that reduce the net positive charge in the active site of Escherichia coli AspRS. Earlier, Glutamine 199 was changed to a negatively‐charged glutamate, giving a computed reduction in Asp affinity in good agreement with experiment. Here, Lysine 198 was changed to a neutral leucine; then, Lys198 and Gln199 were mutated simultaneously. Both mutants are predicted to have reduced Asp binding and improved Asn binding, but the changes are insufficient to overcome the initial, high specificity of the native enzyme, which retains a preference for Asp. Probing the aminoacyl‐adenylation reaction through pyrophosphate exchange experiments, we found no detectable activity for the mutant enzymes, indicating weaker Asp binding and/or poorer transition state stabilization. The simulations show that the mutations' effect is partly offset by proton uptake by a nearby histidine. Therefore, we performed additional simulations where the nearby Histidines 448 and 449 were mutated to neutral or negative residues: (Lys198Leu, His448Gln, His449Gln), and (Lys198Leu, His448Glu, His449Gln). This led to unexpected conformational changes and loss of active site preorganization, suggesting that the AspRS active site has a limited structural tolerance for electrostatic modifications. The data give insights into the complex electrostatic network in the AspRS active site and illustrate the difficulty in engineering charged‐to‐neutral changes of the preferred ligand. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Cysteine 10 is critical for the activity of Ochrobactrum anthropi glutathione transferase and its mutation to alanine causes the preferential binding of glutathione to the H‐site
Authors: Allocati Nerino , Federici Luca , Masulli Michele , Favaloro Bartolo , Di Ilio Carmine 
Published: December 2007

AbstractThe role of the evolutionarily conserved residue Cys10 in Ochrobactrum anthropi glutathione transferase (OaGST) has been examined by replacing it with an alanine. A double mutant C10A/S11A was also prepared. The effect of the replacements on the coniugating and thiotransferase activities, and on the thermal and chemical stability of the enzyme was analyzed. Our data support the view that in OaGST, in contrast with other beta class GSTs that display significant differences in the glutathione‐binding site, Cys10 is a key residue for glutathione coniugating activity. Furthermore, analysis of the OaGST‐Cys10Ala structure, crystallized in the presence of glutathione, reveals that this mutation causes a switch between the high‐affinity G‐site and a low‐affinity H‐site where hydrophobic cosubstrates bind and where we observe the presence of an unexpected glutathione. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Computational prediction of the binding site of proteinase 3 to the plasma membrane
Authors: Hajjar Eric , Mihajlovic Maja , Witko‐Sarsat Véronique , Lazaridis Themis , Reuter Nathalie 
Published: December 2007

AbstractProteinase 3 (PR3) is a neutrophil‐derived serine proteinase localized within cytoplasmic granules which can be released upon activation. PR3 is exposed at the neutrophil plasma membrane where it can mediate proinflammatory effects. Moreover, PR3 membrane expression is of special relevance in patients with Wegener's granulomatosis, a systemic vasculitis presenting anticytoplasmic neutrophil autoantibodies (ANCA) against PR3, which can bind to PR3 expressed at the surface of neutrophils and amplify their activation state. Therefore, it is of special relevance to unravel the molecular mechanisms governing its association with the membrane to be able to modulate it. To this end, we performed molecular dynamics (MD) simulations of PR3 with the implicit membrane model IMM1‐GC to identify its interfacial binding site (IBS). Both the energies and structures resulting from the MD suggest that PR3 associates strongly with anionic membranes. We observe a unique IBS consisting of five basic (R177, R186A, R186B, K187, R222) and six hydrophobic (F165, F166, F224, L223, F184, W218) amino acids. The basic residues provide the driving force to orient PR3 at the membrane surface, so that the hydrophobic residues can anchor into the hydrocarbon region. Energy decomposition and in silico mutations show that only a few residues account for the membrane association. Similar calculations with HNE suggest a different membrane‐binding mechanism. Our results agree with previous experimental observations and this work predicts, for the first time, the structural determinants of the binding of PR3 to membranes. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Solvent‐exposed residues located in the β‐sheet modulate the stability of the tetramerization domain of p53—A structural and combinatorial approach
Authors: Mora Puig , Carbajo Rodrigo J. , Pineda‐Lucena Antonio , Sánchez del Pino Manuel M. , Pérez‐Payá Enrique 
Published: December 2007

AbstractThe role of hydrophobic amino acids in the formation of hydrophobic cores as one of the major driving forces in protein folding has been extensively studied. However, the implication of neutral solvent‐exposed amino acids is less clear and available information is scarce. We have used a combinatorial approach to study the structural relevance of three solvent‐exposed residues (Tyr327, Thr329, and Gln331) located in theβ‐sheet of the tetramerization domain of the tumor suppressor p53 (p53TD). A conformationally defined peptide library was designed where these three positions were randomized. The library was screened for tetramer stability. A set of p53TD mutants containing putative stabilizing or destabilizing residue combinations was synthesized for a thermodynamic characterization. Unfolding experiments showed a wide range of stabilities, with Tm values between 27 and 83°C. Wild type p53TD and some highly destabilized and stabilized mutants were further characterized. Thermodynamic and biophysical data indicated that these proteins were folded tetramers, with the same overall structure, in equilibrium with unfolded monomers. An NMR study confirmed that the main structural features of p53TD are conserved in all the mutants analyzed. The thermodynamic stability of the different p53TD mutants showed a strong correlation with parameters that favor formation and stabilization of the β‐sheet. We propose that stabilization through hydrophobic interactions of key secondary structure elements might be the underlying mechanism for the strong influence of solvent‐exposed residues in the stability of p53TD. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Overexpression, physicochemical characterization, and modeling of a hyperthermophilic pyrococcus furiosus type 2 IPP isomerase
Authors: Dutoit Raphaël , de Ruyck Jérôme , Durisotti Virginie , Legrain Christianne , Jacobs Eric , Wouters Johan 
Published: December 2007

AbstractIn the first step of this study, type 2 isopentenyl diphosphate isomerase (IDI2) from Pyrococcus furiosus (pf‐IDI2), a hyperthermophilic microorganism, was cloned and overexpressed in E. coli. After purification, hyperthermophilic behavior of this protein was approached by means of enzymatic assays and thermal denaturation studies. Compared with the mesophilic Streptococcus pneumoniae IDI2, which unfolds and looses activity above 50°C, pf‐IDI2 is still folded and active at 80°C. Molecular modeling was applied, in a parallel step, to understand the molecular basis of thermal stability. Comparison of IDI2 from S. pneumoniae, T. thermophilus, and P. furiosus suggested that additional charged residues present in the hyperthermophilic enzyme might contribute to its higher thermal stability. This could increase the number of salt bridges between monomers of IDI2 in P. furiosus enzyme and, hence, decrease flexibility of loops or N‐terminal segment, thereby enhancing its thermal stability. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Tandem use of X‐ray crystallography and mass spectrometry to obtain ab initio the complete and exact amino acids sequence of HPBP, a human 38‐kDa apolipoprotein
Authors: Diemer Hélène , Elias Mikael , Renault Frédérique , Rochu Daniel , Contreras‐Martel Carlos , Schaeffer Christine , Van Dorsselaer Alain , Chabriere Eric 
Published: December 2007

AbstractThe Human Phosphate Binding Protein (HPBP) is a serendipitously discovered apolipoprotein from human plasma that binds phosphate. Amino acid sequence relates HPBP to an intriguing protein family that seems ubiquitous in eukaryotes. These proteins, named DING according to the sequence of their four conserved N‐terminal residues, are systematically absent from eukaryotic genome databases. As a consequence, HPBP amino acids sequence had to be first assigned from the electronic density map. Then, an original approach combining X‐ray crystallography and mass spectrometry provides the complete and a priori exact sequence of the 38‐kDa HPBP. This first complete sequence of a eukaryotic DING protein will be helpful to study HPBP and the entire DING protein family. Proteins 2008. © 2007 Wiley‐Liss, Inc.