bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single Nucleotide Polymorphisms in the Coding Region of the Apolipoprotein H (β2‐Glycoprotein I) Gene and their Correlation with the Protein Polymorphism, Anti‐β2Glycoprotein I Antibodies and Cardiolipin Binding: Description of Novel Haplotypes and Their Evolution
Authors: Kamboh M. Ilyas , Sanghera Dharambir K. , Mehdi Haider , Nestlerode Cara S. , Chen Qi , Khalifa Osama , Naqvi Asma , Manzi Susan , Bunker Clareann H. 
Published: July 2004

SummaryApolipoprotein H (APOH), also known as β2‐glycoprotein I, is a major autoantigen for the production of antiphospholipid antibodies (APA) in autoimmune diseases. APA is also recognized by a cryptic epitope generated following the interaction of APOH with anionic phospholipids (PL). The prevalence of APA in the general U.S. white population is about 10%, but it ranges from 30–70% in patients with lupus and antiphospholipid syndrome. Since the structural characterization of APOH from different mammalian species is important to identify the evolutionary conserved regions that may be critical for its function, we have previously determined the chimpanzee APOH gene structure and the prevalence of APA. There are only two amino acid differences between the chimpanzee and human wild type APOH proteins. Chimpanzees have an unusually high prevalence (64%) of APA. There is a common protein polymorphism in the human APOH gene, with the occurrence of four alleles APOH*1, APOH*2, APOH*3 and APOH*4, the latter being present only in blacks. Based on its differential reactivity with an APOH monoclonal antibody, the APOH*3 allele is further divided into APOH*3W (present only in whites) and APOH*3B (present only in blacks). In this study we have screened a large African population (n = 755) to determine the prevalence of APA and the molecular basis of the protein polymorphism. Almost 50% of the Africans were found to be positive for APA. The APOH*3B allele was found to be identical to the chimpanzee's wild type APOH. Novel two‐site or three‐site haplotypes, encoded in the third domain of APOH, explained the molecular basis of the APOH*3B, APOH*3W and APOH*4 alleles. Based on the comparison of the human and chimpanzee APOH DNA sequences, we suggest that the APOH*3W and APOH*4 alleles arose on the ancestral APOH*3B haplotype after the split of human races. We also found that these haplotypes are associated with the occurrence of APA. Recombinant APOH haplotypes, expressed in COS‐1 cells, showed that these mutations also affect the binding of APOH to anionic PL.
Mutagenesis by Transient Misalignment in the Human Mitochondrial DNA Control Region
Authors: Malyarchuk B. A. , Rogozin I. B. 
Published: July 2004

SummaryTo study spontaneous base substitutions in human mitochondrial DNA (mtDNA), we reconstructed the mutation spectra of the hypervariable segments I and II (HVS I and II) using published data on polymorphisms from various human populations. Classification analysis revealed numerous mutation hotspots in HVS I and II mutation spectra. Statistical analysis suggested that strand dislocation mutagenesis, operating in monotonous runs of nucleotides, plays an important role in generating base substitutions in the mtDNA control region. The frequency of mutations compatible with the primer strand dislocation in the HVS I region was almost twice as high as that for template strand dislocation. Frequencies of mutations compatible with the primer and template strand dislocation models are almost equal in the HVS II region. Further analysis of strand dislocation models suggested that an excess of pyrimidine transitions in mutation spectra, reconstructed on the basis of the L‐strand sequence, is caused by an excess of both L‐strand pyrimidine transitions and H‐strand purine transitions. In general, no significant bias toward parent H‐strand‐specific dislocation mutagenesis was found in the HVS I and II regions.
TNR/11q#1 Trinucleotide (GCC)n Repeat Alleles and Predisposition to Acute and Chronic Leukemia
Authors: Klinkov A. A. , Nikitin E. A. , Maiorova O. V. , Ivanov M. A. , Strelnikov V. V. , Babenko O. V. , Zemlyakova V. V. , Kuznetsova E. B. , Zaletayev D. V. 
Published: July 2004

SummaryTNR/11q#1 is a polymorphic trinucleotide (GCC)n repeat located within the minimal region of the 11q deletion in chronic lymphocytic leukemia (CLL). It was recently shown that certain alleles of this repeat are associated with a worse prognosis in CLL patients. To investigate the role of TNR/11q#1 variants as risk‐modifying factors in leukemogenesis, we conducted a case‐control study on 113 acute lymphotic leukemia (ALL) patients, 82 CLL patients and 146 healthy controls of Russian origin. Comparison of allele and genotype distributions in the control, ALL and CLL groups, performed by Fisher's exact test with two‐sized P‐value, showed significant decrease in the presence of the GCC6 allele in the ALL and CLL groups compared to controls. Moreover, ‘rare' alleles GCC7‐8 and GCC13‐14 were significantly overrepresented in the ALL group versus controls. We found that CLL risk genotypes were those with both alleles containing more than 6 GCC repeats (P = 0,0212, odds ratio = 1,68 (95% CI, 1 121… 2,531)). ALL risk genotypes include three allele combination variants: 1) both alleles containing more than 6 GCC repeats (P = 0,0019, odds ratio = 1,756 (95% CI 1,223…2,502)); 2) one of the alleles containing 7 or 8 repeats (P = 0,0155, odds ratio = 18,22 (95% CI 1,93…136.37)); 3) one of the alleles containing more than 12 repeats (P = 0,0209, Odds ratio = 2,599 (95% CI 1,161…5,815)). Association of certain alleles and genotypes of the TNR/11q#1 repeat with both acute and chronic lymphocytic leukemia suggests the presence of a cancer related gene, involved in a wide spectrum of neoplasia, in the vicinity of this repeat.
Prediction of phosphorylation sites using SVMs
Authors: Kim Jong Hun , Lee Juyoung , Oh Bermseok , Kimm Kuchan , Koh InSong 
Published: July 2004

Abstract
Motivation: Phosphorylation is involved in diverse signal transduction pathways. By predicting phosphorylation sites and their kinases from primary protein sequences, we can obtain much valuable information that can form the basis for further research. Using support vector machines, we attempted to predict phosphorylation sites and the type of kinase that acts at each site.
Results: Our prediction system was limited to phosphorylation sites catalyzed by four protein kinase families and four protein kinase groups. The accuracy of the predictions ranged from 83 to 95% at the kinase family level, and 76–91% at the kinase group level. The prediction system used—PredPhospho—can be applied to the functional study of proteins, and can help predict the changes in phosphorylation sites caused by amino acid variations at intra- and interspecies levels.
Availability: PredPhospho is available at http://www.ngri.re.kr/proteo/PredPhospho.htm.
Supplementary information: http://www.ngri.re.kr/proteo/supplementary.doc
Normalization of microarray data using a spatial mixed model analysis which includes splines
Authors: Baird David , Johnstone Peter , Wilson Theresa 
Published: July 2004

Abstract
Motivation: Microarray experiments with thousands of genes on a slide and multiple slides used in any experimental set represent a large body of data with many sources of variation. The identification of such sources of variation within microarray experimental sets is critical for correct deciphering of desired gene expression differences.
Results: We describe new methods for the normalization using spatial mixed models which include splines and analysis of two-colour spotted microarrays for within slide variation and for a series of slides. The model typically explains 45–85% of the variation on a slide with only ∼1% of the total degrees of freedom. The results from our methods compare favourably with those from intensity dependent normalization loess methods where we accounted for twice as much uncontrolled and unwanted variation on the slides. We have also developed an index for each EST that combines the various measures of the differential response into a single value that researchers can use to rapidly assess the genes of interest.
Availability: GenStat code is available from the first author.
Widespread Paleopolyploidy in Model Plant Species Inferred from Age Distributions of Duplicate Genes[W]
Authors: Blanc Guillaume , Wolfe Kenneth H. 
Published: July 2004

AbstractIt is often anticipated that many of today's diploid plant species are in fact paleopolyploids. Given that an ancient large-scale duplication will result in an excess of relatively old duplicated genes with similar ages, we analyzed the timing of duplication of pairs of paralogous genes in 14 model plant species. Using EST contigs (unigenes), we identified pairs of paralogous genes in each species and used the level of synonymous nucleotide substitution to estimate the relative ages of gene duplication. For nine of the investigated species (wheat [Triticum aestivum], maize [Zea mays], tetraploid cotton [Gossypium hirsutum], diploid cotton [G. arboretum], tomato [Lycopersicon esculentum], potato [Solanum tuberosum], soybean [Glycine max], barrel medic [Medicago truncatula], and Arabidopsis thaliana), the age distributions of duplicated genes contain peaks corresponding to short evolutionary periods during which large numbers of duplicated genes were accumulated. Large-scale duplications (polyploidy or aneuploidy) are strongly suspected to be the cause of these temporal peaks of gene duplication. However, the unusual age profile of tandem gene duplications in Arabidopsis indicates that other scenarios, such as variation in the rate at which duplicated genes are deleted, must also be considered.
Variation in Expression and Protein Localization of the PIN Family of Auxin Efflux Facilitator Proteins in Flavonoid Mutants with Altered Auxin Transport inArabidopsis thaliana [W]
Authors: Peer Wendy Ann , Bandyopadhyay Anindita , Blakeslee Joshua J. , Makam Srinivas N. , Chen Rujin J. , Masson Patrick H. , Murphy Angus S. 
Published: July 2004

AbstractAglycone flavonols are thought to modulate auxin transport in Arabidopsis thaliana via an as yet undefined mechanism. Biochemical studies suggest that flavonoids interact with regulatory proteins rather than directly with the PIN auxin efflux facilitator proteins. Auxin transport is enhanced in the absence of flavonoids (transparent testa4 [tt4]) and reduced in the presence of excess flavonols (tt7 and tt3). Steady state PIN mRNA levels in roots inversely correlate with auxin movement in tt mutants. PIN gene transcription and protein localization in flavonoid-deficient mutants appear to be modulated by developmental cues and are auxin responsive. Modulation of PIN gene expression and protein distribution by localized auxin accumulations occurs in the wild type as well. Flavonoids inhibit auxin transport primarily at the shoot apex and root tip and appear to modulate vesicular cycling of PIN1 at the root tip. In some auxin-accumulating tissues, flavonoid increases and changes in flavonoid speciation are subsequent to auxin accumulation.
Heterogeneous Expression Patterns and Separate Roles of theSEPALLATAGeneLEAFY HULL STERILE1in Grasses[W]
Authors: Malcomber Simon T. , Kellogg Elizabeth A. 
Published: July 2004

AbstractSEPALLATA (SEP) genes exhibit distinct patterns of expression and function in the grass species rice (Oryza sativa) and maize (Zea mays), suggesting that the role of the genes has changed during the evolution of the family. Here, we examine expression of the SEP-like gene LEAFY HULL STERILE1 (LHS1) in phylogenetically disparate grasses, reconstruct the pattern of gene expression evolution within the family, and then use the expression patterns to test hypotheses of gene function. Our data support a general role for LHS1 in specifying determinacy of the spikelet meristem and also in determining the identity of lemmas and paleas; these two functions are separable, as is the role of the gene in specifying floret meristems. We find no evidence that LHS1 determines flower number; it is strongly expressed in all spikelet meristems even as they are producing flowers, and expression is not correlated with eventual flower number. LHS1 expression in only the upper flowers of the spikelet appears to be the ancestral state; expression in all flowers is derived in subfamily Pooideae. LHS1 expression in pistils, stamens, and lodicules varies among the cereals. We hypothesize that LHS1 may have affected morphological diversification of grass inflorescences by mediating the expression of different floral identity genes in different regions of the floret and spikelet.
Overexpression ofGLUTAMINE DUMPER1Leads to Hypersecretion of Glutamine from Hydathodes of Arabidopsis Leaves[W]
Authors: Pilot Guillaume , Stransky Harald , Bushey Dean F. , Pratelli Reéjane , Ludewig Uwe , Wingate Vincent P.M. , Frommer Wolf B. 
Published: July 2004

AbstractSecretion is a fundamental process providing plants with the means for disposal of solutes, improvement of nutrient acquisition, and attraction of other organisms. Specific secretory organs, such as nectaries, hydathodes, and trichomes, use a combination of secretory and retrieval mechanisms, which are poorly understood at present. To study the mechanisms involved, an Arabidopsis thaliana activation tagged mutant, glutamine dumper1 (gdu1), was identified that accumulates salt crystals at the hydathodes. Chemical analysis demonstrated that, in contrast with the amino acid mixture normally present in guttation droplets, the crystals mainly contain Gln. GDU1 was cloned and found to encode a novel 17-kD protein containing a single putative transmembrane span. GDU1 is expressed in the vascular tissues and in hydathodes. Gln content is specifically increased in xylem sap and leaf apoplasm, whereas the content of several amino acids is increased in leaves and phloem sap. Selective secretion of Gln by the leaves may be explained by an enhanced release of this amino acid from cells. GDU1 study may help to shed light on the secretory mechanisms for amino acids in plants.
Endoplasmic Reticulum Export Sites and Golgi Bodies Behave as Single Mobile Secretory Units in Plant Cells[W]
Authors: daSilva Luis L.P. , Snapp Erik L. , Denecke Jürgen , Lippincott-Schwartz Jennifer , Hawes Chris , Brandizzi Federica 
Published: July 2004

AbstractIn contrast with animals, plant cells contain multiple mobile Golgi stacks distributed over the entire cytoplasm. However, the distribution and dynamics of protein export sites on the plant endoplasmic reticulum (ER) surface have yet to be characterized. A widely accepted model for ER-to-Golgi transport is based on the sequential action of COPII and COPI coat complexes. The COPII complex assembles by the ordered recruitment of cytosolic components on the ER membrane. Here, we have visualized two early components of the COPII machinery, the small GTPase Sar1p and its GTP exchanging factor Sec12p in live tobacco (Nicotiana tabacum) leaf epidermal cells. By in vivo confocal laser scanning microscopy and fluorescence recovery after photobleaching experiments, we show that Sar1p cycles on mobile punctate structures that track with the Golgi bodies in close proximity but contain regions that are physically separated from the Golgi bodies. By contrast, Sec12p is uniformly distributed along the ER network and does not accumulate in these structures, consistent with the fact that Sec12p does not become part of a COPII vesicle. We propose that punctate accumulation of Sar1p represents ER export sites (ERES). The sites may represent a combination of Sar1p-coated ER membranes, nascent COPII membranes, and COPII vectors in transit, which have yet to lose their coats. ERES can be induced by overproducing Golgi membrane proteins but not soluble bulk-flow cargos. Few punctate Sar1p loci were observed that are independent of Golgi bodies, and these may be nascent ERES. The vast majority of ERES form secretory units that move along the surface of the ER together with the Golgi bodies, but movement does not influence the rate of cargo transport between these two organelles. Moreover, we could demonstrate using the drug brefeldin A that formation of ERES is strictly dependent on a functional retrograde transport route from the Golgi apparatus.
Fanconi Syndrome Caused by Antiepileptic Therapy with Valproic Acid
Authors: Knorr Martin , Schaper Jörg , Harjes Malte , Mayatepek Ertan , Rosenbaum Thorsten 
Published: July 2004

Summary:  Purpose: Valproic acid (VPA) is commonly used as an antiepileptic drug (AED). Regular screening for renal side effects is uncommon. Fanconi syndrome, a generalized dysfunction of renal proximal tubular cells, occurs with some inborn errors of metabolism. In addition, it can be acquired by exposure to several toxic substances. We report a case of Fanconi syndrome after long‐term therapy with VPA. Methods: An 8‐year‐old severely disabled and developmentally retarded boy with epilepsy was treated with VPA over a period of 7 years. He was hospitalized after a status epilepticus with laboratory findings suggesting a Fanconi syndrome. A PubMed‐based worldwide review of the literature revealed that Fanconi syndrome is a rare side effect in children during long‐term VPA treatment. We analyzed all 10 previously published cases by comparing age, underlying diseases, medication, and outcome. Results: Examination revealed metabolic acidosis suggestive of renal tubular malfunction. Based on typical clinical and laboratory findings, an acquired Fanconi syndrome was diagnosed. This was treated with large doses of sodium bicarbonate. After discontinuation of VPA, renal function completely normalized within 2 months. Conclusions: Fanconi syndrome appears to be a rare but severe consequence of long‐term VPA therapy. Therefore patients treated with VPA should be checked regularly for the possible development of VPA‐induced Fanconi syndrome.
Seizure Outcome after Anterior Temporal Lobectomy and Its Predictors in Patients with Apparent Temporal Lobe Epilepsy and Normal MRI
Authors: Sylaja P. N. , Radhakrishnan K. , Kesavadas C. , Sarma P. S. 
Published: July 2004

Summary:  Purpose: Very little reliable information is available regarding the role of anterior temporal lobectomy (ATL), optimal presurgical evaluation strategy, post‐ATL seizure outcome, and the factors that predict the outcome in patients with medically refractory temporal lobe epilepsy (TLE) and normal high‐resolution magnetic resonance imaging (MRI). To be cost‐effective, epilepsy surgery centers in developing countries will have to select candidates for epilepsy surgery by using the locally available technology and expertise. Methods: We reviewed the electroclinical and pathological characteristics and seizure outcome of 17 patients who underwent ATL for medically refractory TLE after being selected for ATL based on a noninvasive selection protocol without the aid of positron emission tomography (PET) or single‐photon emission computed tomography (SPECT), despite a normal preoperative high‐resolution MRI. Results: Seven (41%) patients achieved an excellent seizure outcome; five of them were totally seizure free. An additional five (29%) patients had >75% reduction in seizure frequency. The following pre‐ATL factors predicted an excellent outcome: antecedent history of febrile seizures, strictly unilateral anterior temporal interictal epileptiform discharges (IEDs), and concordant type 1 ictal EEG pattern. All the five patients with pathologically verified hippocampal formation neuronal loss were seizure free. The presence of posterior temporal, bilateral temporal, and generalized IEDs portended unfavorable post‐ATL seizure outcome. Conclusions: A subgroup of patients destined to have an excellent post‐ATL outcome can be selected from MRI‐negative TLE patients by using history and scalp‐recorded interictal and ictal EEG data. The attributes of these patients are antecedent history of febrile seizures, strictly unilateral anterior IEDs, and concordant type 1 ictal EEG pattern.
Estimated Cost of Inpatient Admissions and Outpatient Appointments for a Population with Epilepsy: A Record Linkage Study
Authors: Morgan Christopher Ll. , Kerr Michael P. 
Published: July 2004

Summary:  Purpose: This study describes the hospital costs for a population with epilepsy in 1 year (1999). The study was conducted in a defined geographic United Kingdom population of 424,000. Methods: A register of patients with epilepsy was constructed by using a variety of data sources that had undergone a process of record linkage. Hospital admissions were coded by using Healthcare Resource Group (HRG) and costed by using published National Health Service reference costs. A population of 3,892 people with epilepsy was recorded. Results: The cost of inpatient care for these patients with epilepsy was £2,537,386 ($4,135,939), an excess of £1,598,909 ($2,606,222) compared with the population as a whole. Of this, £320,182 ($521,897) was associated with a primary diagnosis of epilepsy, and £679,757 ($1,108,004) was associated with secondary diagnoses. Outpatient expenditure was £732,823 ($1,194,501). Conclusions: This study demonstrates that people with epilepsy use excess resources and that this is not explained solely by either the direct or indirect effects of their epilepsy. These data may help in understanding of the complex issues surrounding the health economics of epilepsy.
Lateralization of Deficit in Self‐Awareness of Memory in Patients with Intractable Epilepsy
Authors: Andelman Fani , Zuckerman‐Feldhay Einat , Hoffien Danny , Fried Itzhak , Neufeld Miri Y. 
Published: July 2004

Summary:  Purpose: Memory disorders are prominent among patients with intractable epilepsy. It has, however, been frequently observed that subjective memory complaints of these patients did not match their performance on objective memory tests. This discrepancy may reflect emotional, cognitive, or self‐awareness deficits among these individuals. The aim of the current study was to explore the interference of cerebral dysfunction on accuracy of self‐appraisal for memory. Methods: The degree of concordance between self‐perception of memory function, as measured by a visual analogue scale, and actual performance on memory tests was computed in 35 patients who were candidates for epilepsy surgery and demographically matched normal control subjects. The difference between the self‐estimated memory ability and performance on memory tests and its relation to the laterality of an epileptogenic lesion, cognitive factors, and affective status was then examined. Results: The results show that the discrepancy between the self‐estimated memory ability and performance on memory tests in patients with right hemisphere epileptogenic lesions was significantly larger in magnitude compared with that in patients with left hemisphere lesions and demographically matched control subjects (p = 0.001). Furthermore, whereas patients with left hemisphere lesions and normal controls had about an equal number of positive and negative discrepancy scores, all patients with right hemisphere lesions had positive discrepancy scores, suggesting a tendency for overestimation of memory abilities. Conclusions: These results suggest that right hemisphere lesions may introduce a systematic bias in self‐awareness for memory. This bias may color patients' perceptions of self and others, affecting their perceptions of the quality of life, and necessitating an adjustment of the treatment goals and procedures.