bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fold recognition, homology modeling, docking simulations, kinetics analysis and mutagenesis of ATP/CTP:tRNA nucleotidyltransferase from Methanococcus jannaschii
Authors: Bujnicki Janusz M. , Albert Megan A. , Nelson Donald J. , Thurlow David L. 
Published: July 2003

AbstractATP/CTP:tRNA nucleotidyltransferases (NTases) and poly(A) polymerases (PAPs) belong to the same superfamily and their catalytic domains are remotely related. Based on the results of fold‐recognition analysis and comparison of secondary structure patterns, we predicted that these two NTase families share three domains, corresponding to “palm,” “fingers,” and “fingernails” in the PAP crystal structure. A homology model of tRNA NTase from Methanococcus jannaschii was constructed. Energy minimization calculations of enzyme‐nucleotide complexes and computer‐aided docking of nucleotides onto the enzyme's surface were carried out to explore possible ATP and CTP binding sites. Theoretical models were used to guide experimental analysis. Recombinant His‐tagged enzyme was expressed in Escherichia coli, and kinetic properties were characterized. The apparent KM for CTP was determined to be 38 μM, and the apparent KM for ATP was 21 μM. Three mutations of basic amino acids to alanine were created in a highly conserved region predicted to be in the vicinity of the nucleotide binding site. A deletion was also constructed to remove the C‐terminal structural domain defined by the model; it retained about 1% of wild type enzymatic activity using CTP as co‐substrate, confirming that detectable catalytic activity is exhibited by the N‐terminal domain, as defined by the model. Our results suggest a mechanism of differential ATP and CTP binding, which explains how the tRNA NTase, having only one catalytic site, utilizes different nucleotide triphosphates depending on the nature of the tRNA substrate. Proteins 2003;51:349–359. © 2003 Wiley‐Liss, Inc.
A template search reveals mechanistic similarities and differences in β‐ketoacyl synthases (KAS) and related enzymes
Authors: Dawe Jennifer H. , Porter Craig T. , Thornton Janet M. , Tabor Alethea B. 
Published: July 2003

AbstractA detailed comparison of the active sites in β‐ketoacyl synthases (KAS) and related enzymes has been made. Using three‐dimensional templates of the three catalytic residues to scan the protein structural database reveals differences in both the geometry and the catalytic role of equivalent residues in different members of the family. The template based on the catalytic cysteine and two histidines in the KAS I and II is totally specific for this family, with no false hits. However, the role of the histidines in catalysis is different between KAS I/II and thiolase on the one hand and KAS III/chalcone synthase on the other. In contrast, a template comprising only cysteine and one histidine is not specific with many hits including members of the KAS family, metal binding sites, other active sites in nonhomologous proteins, and some “random” nonactive sites. Proteins 2003;52:427–435. © 2003 Wiley‐Liss, Inc.
Deciphering a novel thioredoxin‐like fold family
Authors: Kinch Lisa N. , Baker David , Grishin Nick V. 
Published: July 2003

AbstractSequence ‐ and structure‐based searching strategies have proven useful in the identification of remote homologs and have facilitated both structural and functional predictions of many uncharacterized protein families. We implement these strategies to predict the structure of and to classify a previously uncharacterized cluster of orthologs (COG3019) in the thioredoxin‐like fold superfamily. The results of each searching method indicate that thioltransferases are the closest structural family to COG3019. We substantiate this conclusion using the ab initio structure prediction method rosetta, which generates a thioredoxin‐like fold similar to that of the glutaredoxin‐like thioltransferase (NrdH) for a COG3019 target sequence. This structural model contains the thiol‐redox functional motif CYS‐X‐X‐CYS in close proximity to other absolutely conserved COG3019 residues, defining a novel thioredoxin‐like active site that potentially binds metal ions. Finally, the rosetta‐derived model structure assists us in assembling a global multiple‐sequence alignment of COG3019 with two other thioredoxin‐like fold families, the thioltransferases and the bacterial arsenate reductases (ArsC). Proteins 2003;52:323–331. Published 2003 Wiley‐Liss, Inc.
Comparative analysis of structural properties of the C‐type‐lectin‐like domain (CTLD)
Authors: Zelensky Alex N. , Gready Jill E. 
Published: July 2003

AbstractThe superfamily of proteins containing the C‐type‐lectin‐like domain (CTLD) is a group of abundant extracellular metazoan proteins characterized by evolutionary flexibility and functional versatility. Several CTLDs are also found in parasitic prokaryotes and viruses. The 37 distinct currently available CTLD structures demonstrate significant structural conservation despite low or undetectable sequence similarity. Our aim in this study was to perform an extensive comparative analysis of all available CTLD structures to establish the most conserved structural features of the fold, and to test and extend the early analysis of Drickamer. By implication, these features should be those critical for maintenance of integrity of the fold. By analyzing CTLD structures superimposed by several methods, we have established groups of conserved structural positions involved in fold maintenance but not in ligand binding; these are consistent with the fold's known functional flexibility. In addition to the well‐recognized disulfide bridges, groups of conserved residues are involved in hydrophobic interactions stabilizing the core of the fold and the long loop region, and in an α2‐β1–β5 polar interaction. Evaluation of the conclusions of the structure comparison study compared with alignments of all available human, mouse and Caenorhabditis elegans CTLD sequences showed that conservation patterns are preserved throughout the whole CTLD sequence space. Our observations provide an improved understanding of CTLD structure, and will help in identification of new CTLDs and the mechanisms that drive and constrain the coevolution of the structure and function of the fold. Proteins 2003;52:466–477. © 2003 Wiley‐Liss, Inc.
An Information‐Theoretic Approach to Descriptor Selection for Database Profiling and QSAR Modeling
Authors: Godden Jeffrey W. , Bajorath Jürgen 
Published: July 2003

AbstractIn order to rationalize the selection of molecular descriptors for QSAR and other applications, we have adapted the Shannon entropy concept that was originally developed in digital communication theory. The approach has been extended to facilitate the large‐scale analysis of molecular descriptors and their information content in diverse compound databases. This has enabled us to identify descriptors with consistently high information content. Furthermore, it has been possible to select descriptors that are sensitive to systematic property differences in diverse compound collections (synthetic compounds, natural products, drug‐like molecules, or drugs) and, in addition, to quantify such database‐specific differences. Selection of descriptors based on information content has been proven useful for binary QSAR analysis. In this review, we describe the principles of entropy‐based descriptor selection and discuss different applications.
Neighborhood Behavior. Fuzzy Molecular Descriptors and their Influence on the Relationship between Structural Similarity and Property Similarity
Authors: Horvath Dragos , Mao Boryeu 
Published: July 2003

AbstractThe similarity principle, stating that molecules of similar structure behave similarly, is an important concept in medicinal chemistry. A properly characterized and well‐understood neighborhood behavior of the structural space versus the activity space is fundamental for the application of the similarity principle in computational chemistry. In this work we focus on the utilization of a fuzzy pharmacophore description of molecular similarity and specifically on the influence of fuzzy pharmacophore pattern matching on the neighborhood behavior (NB) of the similarity scoring scheme. NB is defined as a structure‐activity relationship between the intermolecular distances/dissimilarities in the pharmacophore fingerprint structure space and the corresponding activity differences, formally seen as intermolecular distances in the activity spaces. The latter are defined on hand of a wide variety of datasets on pharmacological and physico‐chemical properties and property profiles. We also investigate the clustering behavior (CB), where the structure‐activity relationship is described in terms of distance‐derived associations of compounds into clusters via classical hierarchical clustering procedures. The neighborhood behavior and the cluster behavior provide alternative and complementary criteria for evaluating the pertinence of a molecular similarity metric.
Genetic Neural Networks for Functional Approximation
Authors: Chiu Ting‐Lan , So Sung‐Sau 
Published: July 2003

AbstractQuantitative structure‐activity relationship (QSAR) analysis is a commonly used ligand‐based molecular design method for the lead optimization process in the pharmaceutical industry. Typically, development of a QSAR model goes through the following stages: descriptor generation, function approximation (including feature selection and model construction), and model validation. This article highlights a promising genetic neural network (GNN) method for function approximation in QSAR and reviews its underlying theoretical concepts, techniques, and recent applications.
ChemSpaceShuttle: A tool for data mining in drug discovery by classification, projection, and 3D visualization
Authors: Givehchi Alireza , Dietrich Axel , Wrede Paul , Schneider Gisbert 
Published: July 2003

AbstractThe ChemSpaceShuttle toolbox provides a graphical interface allowing for ligand‐based design of focused compound libraries by means of linear and non‐linear projection techniques and clustering algorithms. The software implements a non‐linear encoder network and non‐linear partial least squares for the projection of high‐dimensional descriptor vectors into a three dimensional space for visualisation. Compound clustering by a self‐organising map (SOM) is incorporated. Visualization can facilitate the selection of compounds with desired properties from large compound libraries. Two sample applications are presented: similarity‐based compound selection for focused library design, and classification of drugs and nondrugs. A version of ChemSpaceShuttle is freely available at URL: http://gecco.org.chemie.uni‐frankfurt.de/gecco.html.
Comparative study of 0.1% olopatadine hydrochloride and 0.5% ketorolac tromethamine in the treatment of seasonal allergic conjunctivitis
Authors: Yaylali Volkan , Demirlenk Ibrahim , Tatlipinar Sinan , Özbay Davut , Esme Arif , Yildirim Cem , Özden Serap 
Published: July 2003

Abstract.Purpose:  To compare the therapeutic effects of two ophthalmic solutions (0.1% olopatadine hydrochloride and 0.5% ketorolac tromethamine) with different pharmacological mechanisms on the clinical signs and Symptoms of seasonal allergic conjunctivitis (SAC).Methods:  Forty patients with the signs and symptoms of SAC (i.e. hyperaemia, itching, mucus discharge, tearing) were included in this placebo‐controlled, randomized, parallel group, single centre study. In group 1 (20 patients) one eye of each patient was treated with olopatadine and the other with placebo. In group 2 (20 patients) one eye of each patient was treated with ketorolac solution and the other with placebo. The principal signs and symptoms of SAC (hyperaemia and itching) were evaluated at 30 mins and at 2, 7 and 15 days.Results:  In group 1, both parameters improved significantly in eyes treated with olopatadine compared with those receiving placebo at all control examinations (all p < 0.05). Similarly, eyes treated with ketorolac showed significant reductions in signs and symptoms compared with those receiving placebo (all p < 0.05). When the clinical parameters of eyes treated with olopatadine were compared with those treated with ketorolac, the mean score of hyperaemia was found to be lower in the olopatadine group, but the difference was not statistically significant (all p > 0.05). However, the itching score was significantly lower in the olopatadine group from the second day through to the end of the study (p < 0.05).Conclusions:  Both olopatadine and ketorolac ophthalmic solutions were found to be effective in alleviating the clinical signs and symptoms of SAC compared to placebo. However, olopatadine reduces ocular itching significantly more than ketorolac.
Familial uveal melanoma: a report on two families and a review of the literature
Authors: Kodjikian Laurent , Nguyen Khôi , Lumbroso Livia , Gauthier‐Villars Marion , Chauvel Pierre , Plauchu Henri , Sterkers Margaret , Devouassoux Mojgan , Grange Jean‐Daniel 
Published: July 2003

Abstract.Purpose:  A total of 69 families affected by uveal melanoma have been reported in the literature. This report describes two additional families. In addition to presenting these cases, which constitute exceptions, the paper reviews the literature.Material and Methods:  Two families, each with two affected members, were analysed in this retrospective study. The pedigree of each family has been pieced together.Results:  Considering the low incidence of familial uveal melanoma in the general population, it seems unlikely that inherited genetic factors are responsible for the condition; this question remains difficult to resolve.Discussion:  The characteristics of each family history are described and compared with the literature data. The mode of possible inheritance is discussed. Both the histopathology and anatomical location are studied, after which we discuss the body of evidence to establish whether there is an inherited cancer predisposition syndrome in patients with familial uveal melanoma.Conclusion:  The statistical likelihood of such an uncommon tumour occurring independently in two or more family members leads us to believe that some cases of familial uveal melanoma may go unrecognized, and that reports on too few families have been published worldwide to prove the existence of a single mendelien gene. However, appropriate tissue samples, such as blood and tumour samples, should be obtained and conserved for present or future cytogenetic and molecular genetic studies.
Bilateral combined retinal and choroidal detachment in antineutrophil cytoplasmic antibody‐positive scleritis
Authors: Non Matthews B , Stavrou Panagiota 
Published: July 2003

Abstract.Purpose:  To describe a rare complication of scleritis in a patient with positive serum antineutrophil cytoplasmic antibodies (ANCA).Methods:  We present a case report of a patient who developed bilateral retinal and choroidal detachment associated with ANCA‐positive scleritis.Results:  Oral steroids alone were insufficient to maintain sustained remission of ocular inflammation. Clinical relapse of the scleritis was associated with ANCA titres becoming positive again. A combination of cyclophosphamide and steroids was successful in achieving control of the intraocular inflammation over a follow‐up period of 18 months.Conclusion:  Bilateral combined retinal and choroidal detachment is a potentially blinding complication of ANCA‐positive scleritis. Monitoring of ANCA titres is useful in the management of the disease.
A comparison of Nd:YAG capsulotomy rate in two different intraocular lenses: AcrySof and Stabibag
Authors: Stordahl Per Bjørn , Drolsum Liv 
Published: July 2003

Abstract.Purpose:  To evaluate the incidence of posterior capsule opacification after implantation of two different intraocular lenses (IOLs), AcrySof® and Stabibag®, by comparing the neodymium:YAG (Nd:YAG) laser capsulotomy rates.Methods:  The medical records of 596 patients (705 eyes) who underwent phacoemulsification and posterior chamber IOL implantation using either AcrySof (n = 335) or Stabibag (n = 370) IOLs during a 1‐year (1999) period were reviewed. Eyes with secondary cataract, combined procedures or operative complications, such as capsule tears, were excluded from the study. The subjects' age, sex, surgeon (two surgeons), and time for Nd:YAG laser capsulotomy were recorded.Results:  The mean follow‐up was 23 months in both IOL groups. There were no statistically significant differences within the two IOL groups regarding sex distribution or surgeon. The mean age in the AcrySof group was 77.0 years compared to 79.2 years in the Stabibag group (p = 0.001). Nd:YAG laser capsulotomy was performed in 7.6% of patients in the Stabibag group compared to 2.7% in the AcrySof group (i.e. at a significantly higher rate) (p = 0.004). Survival analyses demonstrated that age and type of IOL were the only independent predictors of the incidence of capsulotomy.Conclusions:  This study shows that the frequency of eyes with posterior capsule opacification needing capsulotomy was significantly higher in eyes with Stabibag IOLs compared to eyes with AcrySof IOLs.
Comparison of laser interferometry and ultrasound A‐scan in the measurement of axial length
Authors: Goyal R. , North R. V. , Morgan J. E. 
Published: July 2003

Abstract.Aim:  Laser interferometry is a new, non‐contact technique for the measurement of axial length. In this study we compared measurements of axial length obtained with this technique with those obtained with ultrasound (A‐scan). The reproducibility and examiner‐dependency of the two methods were also analysed.Methods:  Patients presenting at the cataract assessment clinic were invited to participate in the study. Axial length measurements were obtained both by contact ultrasound (A‐scan) and by non‐contact laser interferometry (IOLMasterTM V1.1, Carl Zeiss, Jena, Germany). Intraocular lens powers were calculated using both sets of measurements. The coefficient of variation served as a measure of reproducibility.Results:  A total of 100 eyes in 100 patients were evaluated after informed consent had been obtained. Although estimates of axial length obtained with the two techniques were highly correlated, axial lengths obtained with the contact method (mean 23.35 mm, SD 1.81 mm) were consistently lower than those obtained with the non‐contact method (mean 23.55 mm, SD 1.76 mm) and the difference was statistically significant (p < 0.001). The coefficient of variation was lower with laser interferometry (0.1%) than with the ultrasound technique (0.49%).Conclusions:  Different estimates of axial length are obtained using contact and non‐contact techniques, with the latter producing consistently higher measurements than the former. Laser interferometry provides more reproducible results that should improve the accuracy of measurements of axial length in the clinical setting.
Cortical blindness and hepatic encephalopathy
Authors: Ammar T. , Auwzinger G. , Michaelides M. 
Published: July 2003

Abstract.Purpose:  To present a case of permanent cortical blindness (CB) following hepatic encephalopathy.Methods:  Systematic clinical examination and further investigations to elicit the diagnosis.Conclusion:  Complete CB is an uncommon neurological disorder and is rarely persistent. In rare cases of hepatic encephalopathy, the visual cortex may be affected and CB may occur, which resolves following treatment of the hepatic encephalopathy. We report a previously unreported complication involving permanent CB following hepatic encephalopathy in a young man.
A new index to measure the accuracy of refractive operations
Authors: Suominen S. , Pietilä J. , Mäkinen P. , Uusitalo H. 
Published: July 2003

Abstract.Purpose:  To create a new index to help evaluate the accuracy of the outcome of refractive surgery.Methods:  By combining information given by the cross‐cylinder form of surgically induced refractive change (SIRC) and basic methods of vector analysis, we constructed a new index which serves as a tool to evaluate postoperatively the changes achieved by refractive surgery. This new index gives easily understandable numerical values and takes into account changes in both spherical refraction and astigmatism. We demonstrated the use of this index in two study populations consisting of 20 consecutive eyes operated on using two different lasers, Meditec MEL60 and MEL70, respectively.Results:  Although postoperative uncorrected visual acuity (UCVA) and best corrected visual acuity (BCVA) were better in the MEL70 group, the difference of photoefractive keratectomy (PRK) for combined astigmatism and myopia was not statistically significant. Comparison of the changes in refraction achieved by the two lasers indicated that the MEL60 was more accurate; this was also seen when comparing the total index of error between the two groups.Conclusions:  We suggest the use of this total index of error (TIE) in clinical praxis because it provides an easy and accurate method of evaluating the accuracy of refractive operations. These inaccuracies might otherwise go unnoticed if the basic values only (e.g. UCVA, BCVA and haze) were used in postoperative evaluation.
Visually impaired children with posterior ocular malformations: pre‐ and neonatal data and visual functions
Authors: Fahnehjelm Kristina Teär , Jacobson Lena , Hellström Ann , Lewensohn‐Fuchs Ilona , Ygge Jan 
Published: July 2003

Abstract.Aim:  To analyse pre‐ and neonatal data and ocular findings in children with visual impairment caused by posterior ocular malformations.Methods:  Medical records were scrutinized, dried blood spot cards were analysed for virus DNA and ophthalmological assessments were performed in 28 children with optic nerve hypoplasia (ONH) and 10 with optic/chorio‐retinal coloboma.Results:  Prenatal exposure to possible teratogens was documented in 5/28, herpes simplex virus type 1 DNA was identified in the dried blood spot cards of 1/26 children and neonatal hypoglycaemia in 12/28 children with ONH. The time delay from ocular to endocrinological diagnosis and treatment was 3 years. Children with ONH and severe visual impairment had endocrinopathy more often (11/13) than ONH children with better visual functions (5/15). Prenatal exposure to teratogens or neonatal hypoglycaemia was not identified in any of the children with coloboma.Conclusion:  Neonatal hypoglycaemia was common in children with ONH. Severe visual impairment predicted endocrinopathy. Analysis of dried blood spot cards could serve as an additional diagnostic tool in children with ocular malformations.