bluuebunny/crossref_metadata_2025_split huggingface dataset:
Meningioma of the Jugular Foramen: Glomus Jugulare Mimic and Surgical Challenge
Authors: Gilbert M. Erik , Shelton Clough , McDonald Andre , Salzman Karen L. , Harnsberger H. Ric , Sharma Pramod K. , Jensen Randy L. 
Published: December 2003

AbstractObjectives Meningiomas involving the jugular foramen are rare lesions, with approximately 34 cases reported in the English literature. Clinically, these tumors mimic the more common glomus jugulare tumor. After surgical resection, meningiomas have worse cranial nerve outcomes and higher recurrence rates than glomus tumors. There is controversy regarding the selection of surgical approach, particularly with regard to management of the facial nerve. A reliable means of accurate preoperative diagnosis would help surgical planning and patient counseling.Study Design We present a series of six consecutive large jugular foramen meningiomas resected by a single surgeon from 1996 to 2002.Methods Retrospective case series (chart review).Results The preoperative diagnosis was correct in nearly all (6/7) cases on the basis of the characteristic imaging findings seen with a combination of temporal bone dedicated computed tomography and high‐resolution enhanced magnetic resonance imaging. Five of six patients had lateral facial nerve rerouting (infratemporal fossa Fisch type A), and three patients also had posterior rerouting (transcochlear approach with division of greater superficial petrosal nerve). Total tumor removal was accomplished in 83%. One patient suffered recurrence over a mean follow‐up period of 2.5 years. New postoperative vocal cord palsies occurred in 50% of patients, and all required vocal cord medialization. At 1 year, 50% of patients had normal or near normal (House‐Brackmann I or II) facial function. Postoperative cerebrospinal fluid leaks occurred in two patients, and both eventually required ventriculoperitoneal shunts.Conclusions Meningiomas involving the jugular foramen are surgically challenging tumors that pose unique diagnostic issues. The majority of these lesions can be completely resected. A relatively high postoperative complication rate, which can be controlled with appropriate intervention, is seen with these surgeries.
Results With Titanium Ossicular Reconstruction Prostheses
Authors: Gardner Edward K. , Jackson C. Gary , Kaylie David M. 
Published: December 2003

AbstractObjectives/Hypothesis Despite the enthusiasm of recent short‐term reviews, no center in the United States has published results meeting American Academy of Otolaryngology—Head and Neck Surgery guidelines with titanium‐based prostheses. The purpose of the study was threefold. The first purpose was to review results with a titanium prosthesis system in cases meeting American Academy of Otolaryngology—Head and Neck Surgery reporting guidelines. The second was to compare these results with previously published results using non–titanium‐based prostheses. The third was to examine the authors' results for any evidence of a “learning curve.”Study Design Retrospective chart review was performed for the period from February 2000 to August 2001 and for the period from July 2002 to February 2003.Methods Of 313 cases, 130 consecutive cases were identified in the first period and 65 in the second time period. One hundred two patients had adequate follow‐up for published guidelines. All cases were performed by the senior author (c.g.j.). Comparison data were obtained from a previous publication involving the senior author.Results Successful rehabilitation (≤20 dB pure‐tone average air–bone gap) of conductive hearing loss was obtained in 70% of partial ossicular chain reconstructions and 44% of total ossicular chain reconstructions when titanium prostheses were used. Comparison data revealed successful rehabilitation in 48% and 21% of non–titanium‐based partial and total reconstructions, respectively. Postoperative pure‐tone average air–bone gaps were not significantly different when compared with results in the period from July 2002 to February 2003.Conclusion Newer titanium‐based ossicular reconstruction devices represent an improvement over previously used non–titanium‐based prostheses. The authors think that this improvement is realized rapidly because no learning curve existed in their data.
Granular Cell Tumor of the Trachea in Pregnancy: A Case Report and Review of Literature
Authors: Ipakchi Ramin , Zager Warren H. , de Baca Monica E. , Bloedon Esa , McCue Peter A. , Zwillenberg David 
Published: December 2003

AbstractObjectives/Hypothesis The objectives were to present a case report of a woman with recurrent disease during consecutive pregnancies and to discuss the diagnosis and management of granular cell tracheal tumors, with particular attention to pregnancy and hyperestrogenic states.Study Design Case report and literature review.Methods A Medline search and comprehensive review of literature to assess all cases of granular cell tumors of the trachea were compared and collected, with particular attention to individual cases of pregnancy or cases related to the hyperestrogenic state.Results Thirty‐two cases of granular cell tumors of the trachea were found. Only a few cases related to the hyperestrogenic state were obtained. The case report describes a woman with recurrent disease in subsequent pregnancies during the later stages of pregnancy.Conclusion Few cases of granular cell tumors of the trachea have been reported, with even fewer being pregnancy related. The diagnosis and management of these tumors include careful attention to patient symptoms and airway management.
Thermodynamics and stability of a β‐sheet complex: Molecular dynamics simulations on simplified off‐lattice protein models
Authors: Jang Hyunbum , Hall Carol K. , Zhou Yaoqi 
Published: December 2003

AbstractWe have performed discontinuous molecular dynamics simulations of the thermodynamics and stability of a tetrameric β‐sheet complex that contains four identical four‐stranded antiparallel β‐sheet peptides. The potential used in the simulation is a hybrid Go‐type potential characterized by the bias gap parameter g, an artificial measure of the preference of a model protein for its native state, and the intermolecular contact parameter η, which measures the ratio of intermolecular to intramolecular native attractions. Despite the simplicity of the model, a complex set of thermodynamic transitions for the β‐sheet complex is revealed that shows there are three distinct oligomer (partially ordered, ordered, and highly ordered β‐sheet complex) states and four noninteracting monomers phases. The thermodynamic properties of the three oligomer states strongly depend on both the size of the intermolecular contact parameter η and the temperature. The partially ordered β‐sheet complex is made up of four ordered globules and is observed at intermediate to large η at high temperatures. The ordered β‐sheet complex contains four native β‐sheets and is located at small to intermediate η at low temperatures in the phase diagram. The highly ordered β‐sheet complex has fully‐stiff β‐sheet strands, the same as the global energy minimum structure, and is observed for all η at low temperatures.
Understanding the determinants of stability and folding of small globular proteins from their energetics
Authors: Tiana Guido , Simona Fabio , De Mori Giacomo M.S. , Broglia Ricardo A. , Colombo Giorgio 
Published: December 2003

AbstractThe results of minimal model calculations indicate that the stability and the kinetic accessibility of the native state of small globular proteins are controlled by few “hot” sites. By means of molecular dynamics simulations around the native conformation, which describe the protein and the surrounding solvent at the all‐atom level, an accurate and compact energetic map of the native state of the protein is generated. This map is further simplified by means of an eigenvalue decomposition. The components of the eigenvector associated with the lowest eigenvalue indicate which hot sites are likely to be responsible for the stability and for the rapid folding of the protein. The comparison of the results of the model with the findings of mutagenesis experiments performed for four small proteins show that the eigenvalue decomposition method is able to identify between 60% and 80% of these (hot) sites.
Differences in aggregation properties of three site‐specific mutants of recombinant human stefin B
Authors: Kenig Manca , Berbić Selma , Krijes̆torac Aida , Kroon‐Z̆itko Louise , Tus̆ek Magda , Pompe‐Novak Marus̆a , Z̆erovnik Eva 
Published: December 2003

AbstractWe describe expression, purification, and characterization of three site‐specific mutants of recombinant human stefin B: H75W, P36G, and P79S. The far‐ and near‐UV CD spectra have shown that they have similar secondary and tertiary structures to the parent protein. The elution on gel‐filtration suggests that recombinant human stefin B and the P36G variant are predominantly monomers, whereas the P79S variant is a dimer. ANS dye binding, reflecting exposed hydrophobic patches, is highest for the P36G variant, both at pH 5 and 3. ANS dye binding also is increased for stefin B and the other two variants at pH 3. Under the chosen conditions the highest tendency to form amyloid fibrils has been shown for the recombinant human stefin B. The P79S variant demonstrates a longer lag phase and a lower rate of fibril formation, while the P36G variant is most prone to amorphous aggregation. This was demonstrated by ThT fluorescence as a function of time and by transmission electron microscopy.
Thermostability of multidomain proteins: Elongation factors EF‐Tu from Escherichia coli and Bacillus stearothermophilus and their chimeric forms
Authors: Šanderová Hana , Hůlková Marta , Maloň Petr , Kepková Markéta , Jonák Jiří 
Published: December 2003

AbstractRecombinant mesophilic Escherichia coli (Ec) and thermophilic Bacillus stearothermophilus (Bst) elongation factors EF‐Tus, their isolated G‐domains, and six chimeric EF‐Tus composed of domains of either EF‐Tu were prepared, and their GDP/GTP binding activities and thermostability were characterized. BstEF‐Tu and BstG‐domain bound GDP and GTP with affinities in nanomolar and submicromolar ranges, respectively, fully comparable with those of EcEF‐Tu. In contrast, the EcG‐domain bound the nucleotides with much lower, micromolar affinities. The exchange of domains 2 and 3 had essentially no effect on the GDP‐binding activity; all complexes of chimeric EF‐Tus with GDP retained Kd values in the nanomolar range. The final thermostability level of either EF‐Tu was the result of a cooperative interaction between the G‐domains and domains 2 + 3. The G‐domains set up a “basic” level of the thermostability, which was ∼20°C higher with the BstG‐domain than with the EcG‐domain. This correlated with the growth temperature optimum difference of both bacteria and two distinct thermostabilization features of the BstG‐domain: an increase of charged residues at the expense of polar uncharged residues (CvP bias), and a decrease in the nonpolar solvent‐accessible surface area. Domains 2 + 3 contributed by further stabilization of α‐helical regions and, in turn, the functions of the G‐domains to the level of the respective growth temperature optima. Their contributions were similar irrespective of their origin but, with Ecdomains 2 + 3, dependent on the guanine nucleotide binding state. It was lower in the GTP conformation, and the mechanism involved the destabilization of the α‐helical regions of the G‐domain by Ecdomain 2.
PFIT and PFRIT: Bioinformatic algorithms for detecting glycosidase function from structure and sequence
Authors: Kleiger Gary , Panina Ekaterina M. , Mallick Parag , Eisenberg David 
Published: December 2003

AbstractThe identification of the enzymes involved in the metabolism of simple and complex carbohydrates presents one bioinformatic challenge in the post‐genomic era. Here, we present the PFIT and PFRIT algorithms for identifying those proteins adopting the α/β barrel fold that function as glycosidases. These algorithms are based on the observation that proteins adopting the α/β barrel fold share positions in their tertiary structures having equivalent sets of atomic interactions. These are conserved tertiary interaction positions, which have been implicated in both structure and function. Glycosidases adopting the α/β barrel fold share more conserved tertiary interactions than α/β barrel proteins having other functions. The enrichment pattern of conserved tertiary interactions in the glycosidases is the information that PFIT and PFRIT use to predict whether any given α/β barrel will function as a glycosidase or not. Using as a test set a database of 19 glycosidase and 45 nonglycosidase α/β barrel proteins with low sequence similarity, PFIT and PFRIT can correctly predict glycosidase function for 84% of the proteins known to function as glycosidases. PFIT and PFRIT incorrectly predict glycosidase function for 25% of the nonglycosidases. The program PSI‐BLAST can also correctly identify 84% of the 19 glycosidases, however, it incorrectly predicts glycosidase function for 50% of the nonglycosidases (twofold greater than PFIT and PFRIT). Overall, we demonstrate that the structure‐based PFIT and PFRIT algorithms are both more selective and sensitive for predicting glycosidase function than the sequence‐based PSI‐BLAST algorithm.
Protein folding by the effects of macromolecular crowding
Authors: Tokuriki Nobuhiko , Kinjo Masataka , Negi Shigeru , Hoshino Masaru , Goto Yuji , Urabe Itaru , Yomo Tetsuya 
Published: December 2003

AbstractUnfolded states of ribonuclease A were used to investigate the effects of macromolecular crowding on macromolecular compactness and protein folding. The extent of protein folding and compactness were measured by circular dichroism spectroscopy, fluorescence correlation spectroscopy, and NMR spectroscopy in the presence of polyethylene glycol (PEG) or Ficoll as the crowding agent. The unfolded state of RNase A in a 2.4 M urea solution at pH 3.0 became native in conformation and compactness by the addition of 35% PEG 20000 or Ficoll 70. In addition, the effects of macromolecular crowding on inert macromolecule compactness were investigated by fluorescence correlation spectroscopy using Fluorescence‐labeled PEG as a test macromolecule. The size of Fluorescence‐labeled PEG decreased remarkably with an increase in the concentration of PEG 20000 or Ficoll 70. These results show that macromolecules are favored compact conformations in the presence of a high concentration of macromolecules and indicate the importance of a crowded environment for the folding and stabilization of globular proteins. Furthermore, the magnitude of the effects on macromolecular crowding by the different sizes of background molecules was investigated. RNase A and Fluorescence‐labeled PEG did not become compact, and had folded conformation by the addition of PEG 200. The effect of the chemical potential on the compaction of a test molecule in relation to the relative sizes of the test and background molecules is also discussed.
Active‐site alkylation destabilizes human O6‐alkylguanine DNA alkyltransferase
Authors: Rasimas Joseph J. , Dalessio Paula A. , Ropson Ira J. , Pegg Anthony E. , Fried Michael G. 
Published: December 2003

AbstractO6‐alkylguanine‐DNA alkyltransferase (AGT) repairs pro‐mutagenic O6‐alkylguanine and O4‐alkylthymine lesions in DNA. The alkylated form of the protein is not reactivated; instead, it is rapidly ubiquitinated and degraded. Here, we show that alkylation destabilizes the native fold of the protein by 0.5–1.2 kcal/mole and the DNA‐binding function by 0.8–1.4 kcal/mole. On this basis, we propose that destabilization of the native conformational ensemble acts as a signal for ubiquitination.
Intrasteric control of AMPK via the γ1 subunit AMP allosteric regulatory site
Authors: Adams Julian , Chen Zhi‐Ping , Van Denderen Bryce J.W. , Morton Craig J. , Parker Michael W. , Witters Lee A. , Stapleton David , Kemp Bruce E. 
Published: December 2003

AbstractAMP‐activated protein kinase (AMPK) is a αβγ heterotrimer that is activated in response to both hormones and intracellular metabolic stress signals. AMPK is regulated by phosphorylation on the α subunit and by AMP allosteric control previously thought to be mediated by both α and γ subunits. Here we present evidence that adjacent γ subunit pairs of CBS repeat sequences (after Cystathionine Beta Synthase) form an AMP binding site related to, but distinct from the classical AMP binding site in phosphorylase, that can also bind ATP. The AMP binding site of the γ1 CBS1/CBS2 pair, modeled on the structures of the CBS sequences present in the inosine monophosphate dehydrogenase crystal structure, contains three arginine residues 70, 152, and 171 and His151. The yeast γ homolog, snf4 contains a His151Gly substitution, and when this is introduced into γ1, AMP allosteric control is substantially lost and explains why the yeast snf1p/snf4p complex is insensitive to AMP. Arg70 in γ1 corresponds to the site of mutation in human γ2 and pig γ3 genes previously identified to cause an unusual cardiac phenotype and glycogen storage disease, respectively. Mutation of any of AMP binding site Arg residues to Gln substantially abolishes AMP allosteric control in expressed AMPK holoenzyme. The Arg/Gln mutations also suppress the previously described inhibitory properties of ATP and render the enzyme constitutively active. We propose that ATP acts as an intrasteric inhibitor by bridging the α and γ subunits and that AMP functions to derepress AMPK activity.
N‐linked glycosylation of dipeptidyl peptidase IV (CD26): Effects on enzyme activity, homodimer formation, and adenosine deaminase binding
Authors: Aertgeerts Kathleen , Ye Sheng , Shi Lihong , Prasad Sridhar G. , Witmer Darbi , Chi Ellen , Sang Bi‐Ching , Wijnands Robert A. , Webb David R. , Swanson Ronald V. 
Published: December 2003

AbstractThe type II transmembrane serine protease dipeptidyl peptidase IV (DPPIV), also known as CD26 or adenosine deaminase binding protein, is a major regulator of various physiological processes, including immune, inflammatory, nervous, and endocrine functions. It has been generally accepted that glycosylation of DPPIV and of other transmembrane dipeptidyl peptidases is a prerequisite for enzyme activity and correct protein folding. Crystallographic studies on DPPIV reveal clear N‐linked glycosylation of nine Asn residues in DPPIV. However, the importance of each glycosylation site on physiologically relevant reactions such as dipeptide cleavage, dimer formation, and adenosine deaminase (ADA) binding remains obscure. Individual Asn→Ala point mutants were introduced at the nine glycosylation sites in the extracellular domain of DPPIV (residues 39–766). Crystallographic and biochemical data demonstrate that N‐linked glycosylation of DPPIV does not contribute significantly to its peptidase activity. The kinetic parameters of dipeptidyl peptidase cleavage of wild‐type DPPIV and the N‐glycosylation site mutants were determined by using Ala‐Pro‐AFC and Gly‐Pro‐pNA as substrates and varied by <50%. DPPIV is active as a homodimer. Size‐exclusion chromatographic analysis showed that the glycosylation site mutants do not affect dimerization. ADA binds to the highly glycosylated β‐propeller domain of DPPIV, but the impact of glycosylation on binding had not previously been determined. Our studies indicate that glycosylation of DPPIV is not required for ADA binding. Taken together, these data indicate that in contrast to the generally accepted view, glycosylation of DPPIV is not a prerequisite for catalysis, dimerization, or ADA binding.
Packing, specificity, and mutability at the binding interface between the p160 coactivator and CREB‐binding protein
Authors: Demarest Stephen J. , Deechongkit Songpon , Jane Dyson H. , Evans Ronald M. , Wright Peter E. 
Published: December 2003

AbstractAmong the most common interaction motifs between nuclear proteins is the recognition of one or more amphipathic helices. In an effort to determine principles behind this recognition, we have investigated the interaction between the p160 coactivator protein ACTR and the ACTR‐binding domain of the CREB‐binding protein, CBP. The two proteins use relatively small portions of their primary sequences to form a single synergistically folded domain consisting of six intertwined α‐helices, three from each protein. Neither of the component polypeptides forms a cooperatively folded domain in isolation. However, a considerable amount of residual secondary structure remains in the isolated CBP domain according to CD spectroscopy. Chemical denaturation, differential scanning calorimetry, and ANS binding experiments demonstrate that the isolated CBP domain is not entirely unfolded but forms a helical state with the characteristics of a molten globule. Mutations probing the functional and energetic significance of a buried intermolecular Arg–Asp salt bridge in the interface of the protein complex suggest that these residues are tuned for functional discrimination and not strictly for binding affinity or stability. These results suggest a mechanism for formation of the complex where the unfolded ACTR domain interacts with the partly folded CBP domain in a rapid and specific manner to form the final stable complex.
Refinement of homology‐based protein structures by molecular dynamics simulation techniques
Authors: Fan Hao , Mark Alan E. 
Published: December 2003

AbstractThe use of classical molecular dynamics simulations, performed in explicit water, for the refinement of structural models of proteins generated ab initio or based on homology has been investigated. The study involved a test set of 15 proteins that were previously used by Baker and coworkers to assess the efficiency of the ROSETTA method for ab initio protein structure prediction. For each protein, four models generated using the ROSETTA procedure were simulated for periods of between 5 and 400 nsec in explicit solvent, under identical conditions. In addition, the experimentally determined structure and the experimentally derived structure in which the side chains of all residues had been deleted and then regenerated using the WHATIF program were simulated and used as controls. A significant improvement in the deviation of the model structures from the experimentally determined structures was observed in several cases. In addition, it was found that in certain cases in which the experimental structure deviated rapidly from the initial structure in the simulations, indicating internal strain, the structures were more stable after regenerating the side‐chain positions. Overall, the results indicate that molecular dynamics simulations on a tens to hundreds of nanoseconds time scale are useful for the refinement of homology or ab initio models of small to medium‐size proteins.