bluuebunny/crossref_metadata_2025_split huggingface dataset:
Markedly elevated serum biotinidase activity may indicate glycogen storage disease type Ia
Authors: Wolf B. , Freehauf C. L. , Thomas J. A. , Gordon P. L. , Greene C. L. , Ward J. C. 
Published: December 2003

AbstractSummary: We report two children who presented with symptoms suggestive of biotinidase deficiency. Rather than deficiency, markedly elevated serum biotinidase activities were found. Based upon literature reports of elevated biotinidase activities in children with glycogen storage disease (GSD) type Ia, we considered the latter in our differential diagnosis and subsequently confirmed GSD type Ia in both patients by enzymatic testing. GSD type Ia should be considered in children with markedly elevated serum biotinidase activity.
Niemann–Pick disease: Sixteen‐year follow‐up of allogeneic bone marrow transplantation in a type B variant
Authors: Victor S. , Coulter J. B. S. , Besley G. T. N. , Ellis I. , Desnick R. J. , Schuchman E. H. , Vellodi A. 
Published: December 2003

AbstractSummary: Allogenic bone marrow transplantation (BMT) was carried out on a 3‐year‐old white caucasian girl with Niemann–Pick disease (NPD) type B. The donor was her unaffected brother. The patient was neurologically normal at the time of transplantation. Engraftment was based on cytogenetic studies and increased leukocyte acid sphingomyelinase (ASM) activity. However, liver biopsies taken up to 33 months post transplantation showed only a moderate reduction in stored sphingomyelin and no significant increase in ASM activity. The post‐transplantation period was complicated by severe graft‐versus‐host disease and a respiratory arrest. By 6 years of age, neurological involvement was observed, including bilateral cherry red spots. The proband is now severely mentally and physically disabled. Liver cirrhosis has continued to progress despite the BMT, and haematemesis due to portal hypertension occurred at 17 years of age. However, pulmonary infiltration regressed after BMT and there has been no clinical evidence of pulmonary insufficiency.
Analysis of organic acids after incubation with (16‐2H3)palmitic acid in fibroblasts from patients with mitochondrial β‐oxidation defects
Authors: Osorio J. H. , Lluch M. , Ribes A. 
Published: December 2003

AbstractSummary: The analysis of acylcarnitines as products of incubation of intact fibroblasts with isotope‐labelled precursors, usually (16‐2H3)hexadecanoic acid, is an advanced in vitro method for the study of mitochondrial β‐oxidation defects. We propose a technique for the measurement of the organic acid intermediates after hydrolysis of the acylcarnitines using electron‐impact gas chromatography–mass spectrometry. For some mitochondrial β‐oxidation deficiencies, the characteristic profile enables us to approach the diagnosis with clear differentiation.
Glycine N‐methyltransferase deficiency: A new patient with a novel mutation
Authors: Augoustides‐Savvopoulou P. , Luka Z. , Karyda S. , Stabler S. P. , Allen R. H. , Patsiaoura K. , Wagner C. , Mudd S. H. 
Published: December 2003

AbstractSummary: We report studies of a Greek boy of gypsy origin that show that he has severe deficiency of glycine N‐methyltransferase (GNMT) activity due to apparent homozygosity for a novel mutation in the gene encoding this enzyme that changes asparagine‐140 to serine. At age 2 years he was found to have mildly elevated serum liver transaminases that have persisted to his present age of 5 years. At age 4 years, hypermethioninaemia was discovered. Plasma methionine concentrations have ranged from 508 to 1049 µmol/L. Several known causes of hypermethioninaemia were ruled out by studies of plasma metabolites: tyrosinaemia type I by a normal plasma tyrosine and urine succinylacetone; cystathionine β‐synthase deficiency by total homocysteine of 9.4–12.1 µmol/L; methionine adenosyltransferase I/III deficiency by S‐adenosylmethionine (AdoMet) levels elevated to 1643–2222 nmol/L; and S‐adenosylhomocysteine (AdoHcy) hydrolase deficiency by normal AdoHcy levels. A normal plasma N‐methylglycine concentration in spite of elevated AdoMet strongly suggested GNMT deficiency. Molecular genetic studies identified a missense mutation in the coding region of the boy's GNMT gene, which, upon expression, retained only barely detectable catalytic activity. The mild hepatitis‐like manifestations in this boy are similar to those in the only two previously reported children with GNMT deficiency, strengthening the likelihood of a causative association. Although his deficiency of GNMT activity may well be more extreme, his metabolic abnormalities are not strikingly greater. Also discussed is the metabolic role of GNMT; several additional metabolite abnormalities found in these patients; and remaining questions about human GNMT deficiency, such as the long‐term prognosis, whether other individuals with this defect are currently going undetected, and means to search for such persons.
Identification of a common mutation (Gly194Cys) in both Arab Moslem and Ashkenazi Jewish patients with dihydrolipoamide dehydrogenase (E3) deficiency: Possible beneficial effect of vitamin therapy
Authors: Hong Y. S. , Korman S. H. , Lee J. , Ghoshal P. , Wu Q. , Barash V. , Kang S. , Oh S. , Kwon M. , Gutman A. , Rachmel A. , Patel M. S. 
Published: December 2003

AbstractSummary: Dihydrolipoamide dehydrogenase (E3) deficiency with a clinical phenotype and genotype (Gly194Cys homozygous), previously identified only in Ashkenazi Jewish patients, was diagnosed in two Palestinian Arab siblings and two unrelated Ashkenazi Jewish patients. While three of the four patients died in childhood without specific treatment, the surviving patient at age 18 years may have benefited from long‐term daily supplementation with a cocktail of riboflavin, biotin, coenzyme Q and carnitine.
NO/cyclic GMP pathway mediates the relaxation of feline lower oesophageal sphincter
Authors: Jun C. H. , Lee T. S. , Sohn U. D. 
Published: December 2003

Summary1 We examined the role of the NO/cyclic GMP (cyclic GMP) pathway in nitric oxide (NO)‐ and vasoactive intestinal peptide (VIP)‐induced relaxation of feline lower oesophageal sphincter (LES). Furthermore, it was studied whether methylene blue, LY83583 and ODQ, which are soluble guanylate cyclase (sGC) inhibitors, could inhibit NO‐induced relaxation.2 The nitric oxide synthase (NOS) inhibitor, N‐nitro‐l‐arginine (l‐NNA) had no effect in sodium nitropruside (SNP)‐induced relaxation, but 3‐morpholinosydnonimine‐N‐ethylcarbamide (SIN‐1)‐induced relaxation was decreased by the pretreatment of l‐NNA, which showed that SIN‐1, not SNP, could activate NOS to cause relaxation. Methylene blue and LY83583 did not inhibit the relaxation by SNP and SIN‐1. However, the more specific sGC inhibitor ODQ blocked the relaxation induced by NO donors.3 To identify the relationship of NOS, sGC and adenylate cyclase in VIP‐induced relaxation, tissue were pretreated with l‐NNA and ODQ and SQ22536. These inhibitors produced significant inhibition of this response to VIP. The adenylyl cyclase inhibitor SQ 22536 also inhibited relaxation by VIP.4 In conclusion, our data showed that SNP‐ and SIN‐1‐induced relaxation was mediated by sGC. Of sGC inhibitors, methylene blue and LY83583 were not adequate for the examination of NO donor‐induced feline LES smooth muscle relaxation. VIP also caused relaxation by the pathway involving NO and cGMP and cAMP.
Opposite effects of endogenous nitric oxide and prostaglandin F2α in the rat mesenteric bed
Authors: Peredo H. A. 
Published: December 2003

Summary1 The relationship between the effects of endogenous nitric oxide (NO) and prostanoids on the noradrenaline (NA)‐induced contractions and the mechanisms involved were investigated in the rat perfused mesenteric bed, using NG‐nitro‐l‐arginine methyl ester (l‐NAME), a NO synthase inhibitor and sodium nitroprusside (SNP), a NO donor.2 The constrictor responses to NA were reduced to 50% by the cyclooxygenase inhibitor 10 μm indomethacin as well as by 1 μm SNP. When indomethacin and SNP were perfused simultaneously the contractions were further reduced.3 The NA‐induced contractions were increased by the addition of 400 μml‐NAME and the addition of either indomethacin or SNP abolished such increases. The simultaneous perfusion of both agents further reduced the contractions.4 Removal of the endothelium increased NA‐induced contractions to a similar extent as l‐NAME and this increase was abolished by indomethacin as well as by SNP.5 The perfusion of 10 μm NA augmented the release of prostaglandin (PG) F2α by the mesenteric bed without modifications in any other prostanoid. In the presence of l‐NAME, this effect was further increased. However, SNP abolished the NA‐induced stimulation of PGF2α release.6 In de‐endothelialized preparations NA also stimulated PGF2α production as observed in intact preparations. This effect was more marked in the presence of l‐NAME; in contrast, SNP abolished the stimulation.7 In conclusion, the present results suggest an opposite action between NO and PGF2α on the NA‐induced contractions in the rat mesenteric bed.
Protein β-turn prediction using nearest-neighbor method
Authors: Kim Saejoon 
Published: December 2003

Abstract
Motivation: With the emerging success of protein secondary structure prediction through the applications of various statistical and machine learning techniques, similar techniques have been applied to protein β-turn prediction. In this study, we perform protein β-turn prediction using a k-nearest neighbor method, which is combined with a filter that uses predicted protein secondary structure information. Traditional β-turn prediction from k-nearest neighbor method is modified to account for the unbalanced ratio of the natural occurrence of β-turns and non-β-turns.
Results: Our prediction scheme is tested on a set of 426 non-homologous protein sequences. The prediction scheme consists of two stages: k-nearest neighbor method stage and filtering stage. Variations of the k-nearest neighbor method were used to take property of β-turns into consideration. Our filtering method uses β-turn/non-β-turn estimates from the k-nearest neighbor method stage and predicted protein secondary structure information from PSI-PRED in order to get new β-turn/non-β-turn estimate. Our result is compared with the previously best known β-turn prediction method on the dataset of 426 non-homologous protein sequences and is shown to give slightly superior performance at significantly lower computational complexity.
Availability: Contact the author for information on the source code of the programs used.
ClusPro: an automated docking and discrimination method for the prediction of protein complexes
Authors: Comeau Stephen R. , Gatchell David W. , Vajda Sandor , Camacho Carlos J. 
Published: December 2003

Abstract
Motivation: Predicting protein interactions is one of the most challenging problems in functional genomics. Given two proteins known to interact, current docking methods evaluate billions of docked conformations by simple scoring functions, and in addition to near-native structures yield many false positives, i.e. structures with good surface complementarity but far from the native.
Results: We have developed a fast algorithm for filtering docked conformations with good surface complementarity, and ranking them based on their clustering properties. The free energy filters select complexes with lowest desolvation and electrostatic energies. Clustering is then used to smooth the local minima and to select the ones with the broadest energy wells—a property associated with the free energy at the binding site. The robustness of the method was tested on sets of 2000 docked conformations generated for 48 pairs of interacting proteins. In 31 of these cases, the top 10 predictions include at least one near-native complex, with an average RMSD of 5 Å from the native structure. The docking and discrimination method also provides good results for a number of complexes that were used as targets in the Critical Assessment of PRedictions of Interactions experiment.
Availability: The fully automated docking and discrimination server ClusPro can be found at http://structure.bu.edu
Light-weight integration of molecular biological databases
Authors: Philippi Stephan 
Published: December 2003

Abstract
Motivation: Due to the increasing number of molecular biological databases and the exponential growth of their contents, database integration is an important topic of research in bioinformatics. Existing approaches in this area have in common that considerable efforts are needed to provide integrated access to heterogeneous data sources.
Results: This article describes the LIMBO architecture as a light-weight approach to molecular biological database integration. By building systems upon this architecture, the efforts needed for database integration can be significantly lowered.
Availability: As an illustration of the principle usefulness of the underlying ideas, a prototypical implementation based upon the LIMBO architecture is described. This implementation is exclusively based on freely available open source components like the PostgreSQL database management system and the BioRuby project. Additional files and modified components are available upon request from the author.
An Iterated loop matching approach to the prediction of RNA secondary structures with pseudoknots
Authors: Ruan Jianhua , Stormo Gary D. , Zhang Weixiong 
Published: December 2003

Abstract
Motivation: Pseudoknots have generally been excluded from the prediction of RNA secondary structures due to its difficulty in modeling. Although, several dynamic programming algorithms exist for the prediction of pseudoknots using thermodynamic approaches, they are neither reliable nor efficient. On the other hand, comparative methods are more reliable, but are often done in an ad hoc manner and require expert intervention. Maximum weighted matching, an algorithm for pseudoknot prediction with comparative analysis, suffers from low-prediction accuracy in many cases.
Results: Here we present an algorithm, iterated loop matching, for reliably and efficiently predicting RNA secondary structures including pseudoknots. The method can utilize either thermodynamic or comparative information or both, thus is able to predict pseudoknots for both aligned and individual sequences. We have tested the algorithm on a number of RNA families. Using 8–12 homologous sequences, the algorithm correctly identifies more than 90% of base-pairs for short sequences and 80% overall. It correctly predicts nearly all pseudoknots and produces very few spurious base-pairs for sequences without pseudoknots. Comparisons show that our algorithm is both more sensitive and more specific than the maximum weighted matching method. In addition, our algorithm has high-prediction accuracy on individual sequences, comparable with the PKNOTS algorithm, while using much less computational resources.
Availability: The program has been implemented in ANSI C and is freely available for academic use at http://www.cse.wustl.edu/~zhang/projects/rna/ilm/
Supplementary information: http://www.cse.wustl.edu/~zhang/projects/rna/ilm/
Distribution of words with a predefined range of mismatches to a DNA probe in bacterial genomes
Authors: Melko O. Michael , Mushegian Arcady R. 
Published: December 2003

Abstract
Motivation: Hybridization of oligonucleotides with longer nucleotide sequences is an essential step in nucleic acid biosynthesis in vitro and in vivo, in oligonucleotide-based diagnostics, and in therapeutic applications of oligonucleotides. A major factor determining sensitivity and selectivity of hybridization is the number of base pair mismatches that occur in an ungapped alignment of the oligonucleotide (probe) and a longer sequence (target).
Results: The k-distance match count between the probe and the target is defined as the number of ungapped alignments between the two sequences that have exactly k mismatches, and the k-neighbor match count is defined as the sum of the j-distance match counts for j between 0 and k. We derive a novel formula for the probability of a k-distance match. This formula is based on the assumption that the target is strand-symmetric Bernoulli text (i.e. nucleotides are independently, identically distributed in the target and satisfy Chargaff's second parity rule). Our model predicts that the GC-content in both the probe and the target significantly affects the match count expectation. The ratio of k-neighbor match counts in two distinct genomes for a given probe is a measure of its specificity. We calculated such ratios for pairs of bacterial genomes with different combinations of length, GC-content and phylogenetic distance. Examination of the extreme values of these ratios indicates that probes with a high discriminative power exist for each tested pair.
Supplementary information: Stowers Institute Technical Report No. 0002, C++ source code, Mathematica notebooks and other information is available at http://www.stowers-institute.org/labs/bioinformatics/omm/index.htm
MedBlast: searching articles related to a biological sequence
Authors: Tu Qiang , Tang Haixu , Ding Dafu 
Published: December 2003

Abstract
Summary: In the genomic era, researchers often want to know more information about a biological sequence by retrieving its related articles. However, there is no available tool yet to achieve conveniently this goal. Here we developed a new literature-mining tool MedBlast, which uses natural language processing techniques, to retrieve the related articles of a given sequence. An online server of this program is also provided.
Availability: Both online server and the program are available freely at http://medblast.sibsnet.org
VizStruct: exploratory visualization for gene expression profiling
Authors: Zhang Li , Zhang Aidong , Ramanathan Murali 
Published: December 2003

Abstract
Motivation: DNA arrays provide a broad snapshot of the state of the cell by measuring the expression levels of thousands of genes simultaneously. Visualization techniques can enable the exploration and detection of patterns and relationships in a complex data set by presenting the data in a graphical format in which the key characteristics become more apparent. The dimensionality and size of array data sets however present significant challenges to visualization. The purpose of this study is to present an interactive approach for visualizing variations in gene expression profiles and to assess its usefulness for classifying samples.
Results: The first Fourier harmonic projection was used to map multi-dimensional gene expression data to two dimensions in an implementation called VizStruct. The visualization method was tested using the differentially expressed genes identified in eight separate gene expression data sets. The samples were classified using the oblique decision tree (OC1) algorithm to provide a procedure for visualization-driven classification. The classifiers were evaluated by the holdout and the cross-validation techniques. The proposed method was found to achieve high accuracy.
Availability: Detailed mathematical derivation of all mapping properties as well as figures in color can be found as supplementary on the web page http://www.cse.buffalo.edu/DBGROUP/bioinformatics/supplementary/vizstruct. All programs were written in Java and Matlab and software code is available by request from the first author.
Twelve C2H2 zinc-finger genes on human chromosome 19 can be each translated into the same type of protein after frameshifts
Authors: Meng Shao-Wu , Zhang Zhuo , Li Jinyan 
Published: December 2003

Abstract
We report a discovery that, of the 226 C2H2 zinc-finger (C2H2-ZNF) genes on human chromosome 19, 12 genes each have two open reading frames (ORFs) that are in different reading frames but that can be translated into the same type of C2H2-ZNF proteins. We came to this observation after using standard tools in an original manner. First, we found that the both ORFs of such a gene contained the same type of significant C2H2-ZNF domain with e-values of e–2 or better. Second, the both ORFs had a promoter, a transcription start site, a start codon, a Kozak pattern and a poly(A) site; hence, each of them can be viewed as a gene in terms of a gene's primary structure. Third, both the ORFs matched not only human C2H2-ZNF expressed sequence tags (ESTs) but also human C2H2-ZNF proteins with e-values of e–50 or better. This indicates that the both ORFs can be transcribed and translated into the same zinc-finger proteins. More importantly, we observed that the phenomenon—a DNA can be translated into the same type of proteins after a frameshift—also occurred in a set of 160 human C2H2-ZNF ESTs and in a set of nine cDNAs of human C2H2-ZNF proteins. This observation based on the two sets of wet-experimental data much strengthened our confidence on the discovery. Our discovery is useful in the deeper understanding of a gene's regulatory mechanism to maintain its function.
Supplementary information: http://zfgene.i2r.a-star.edu.sg
Adjustment of systematic microarray data biases
Authors: Benito Monica , Parker Joel , Du Quan , Wu Junyuan , Xiang Dong , Perou Charles M. , Marron J. S. 
Published: December 2003

Abstract
Motivation: Systematic differences due to experimental features of microarray experiments are present in most large microarray data sets. Many different experimental features can cause biases including different sources of RNA, different production lots of microarrays or different microarray platforms. These systematic effects present a substantial hurdle to the analysis of microarray data.
Results: We present here a new method for the identification and adjustment of systematic biases that are present within microarray data sets. Our approach is based on modern statistical discrimination methods and is shown to be very effective in removing systematic biases present in a previously published breast tumor cDNA microarray data set. The new method of ‘Distance Weighted Discrimination (DWD)’ is shown to be better than Support Vector Machines and Singular Value Decomposition for the adjustment of systematic microarray effects. In addition, it is shown to be of general use as a tool for the discrimination of systematic problems present in microarray data sets, including the merging of two breast tumor data sets completed on different microarray platforms.
Availability: Matlab software to perform DWD can be retrieved from https://genome.unc.edu/pubsup/dwd/
Supplementary information: The complete figures that represent the cluster diagrams in Figure 6 and other figures are available at https://genome.unc.edu/pubsup/dwd/
The Genomic Threading Database
Authors: McGuffin Liam J. , Street Stefano , Sørensen Søren-Aksel , Jones David T. 
Published: December 2003

Abstract
Summary: The Genomic Threading Database currently contains structural annotations for the genomes of over 100 recently sequenced organisms. Annotations are carried out by using our modified GenTHREADER software and through implementing grid technology.
Availability: http://bioinf.cs.ucl.ac.uk/GTD
Supplementary information: http://bioinf.cs.ucl.ac.uk/GTD/demo.avi, http://bioinf.cs.ucl.ac.uk/GTD/summaryView.html, http://bioinf.cs.ucl.ac.uk/GTD/figure1.pdf, http://www.e-protein.org