bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic disorders affecting white matter in the pediatric age
Authors: Di Rocco Maja , Biancheri Roberta , Rossi Andrea , Filocamo Mirella , Tortori‐Donati Paolo 
Published: May 2004

AbstractPediatric white matter disorders can be distinguished into well‐defined leukoencephalopathies, and undefined leukoencephalopathies. The first category may be subdivided into: (a) hypomyelinating disorders; (b) dysmyelinating disorders; (c) leukodystrophies; (d) disorders related to cystic degeneration of myelin; and (e) disorders secondary to axonal damage. The second category, representing up to 50% of leukoencephalopathies in childhood, requires a multidisciplinar approach in order to define novel homogeneous subgroups of patients, possibly representing “new genetic disorders” (such as megalencephalic leukoencepahlopathy with subcortical cysts and vanishing white matter disease that have recently been identified). In the majority of cases, pediatric white matter disorders are inherited diseases. An integrated description of the clinical, neuroimaging and pathophysiological features is crucial for categorizing myelin disorders and better understanding their genetic basis. A review of the genetic disorders affecting white matter in the pediatric age, including some novel entities, is provided. © 2004 Wiley‐Liss, Inc.
Linkage of eye movement dysfunction to chromosome 6p in schizophrenia: Additional evidence
Authors: Matthysse Steven , Holzman Philip S. , Gusella James F. , Levy Deborah L. , Harte Christopher B. , Jørgensen Åge , Møller Lise , Parnas Josef 
Published: May 2004

AbstractEstablishing the genetics of physiological traits associated with schizophrenia may be an important first step in building a neurobiological bridge between the disease phenotype and its genetic underpinnings. One of the best known of the traits associated with schizophrenia is a disorder of smooth pursuit eye tracking (ETD), which is present in 50–80% of schizophrenia patients. ETD is more than three times more prevalent in the families of a schizophrenia patient than is schizophrenia itself. Arolt et al. [1999] estimated LOD scores for ETD of 2.85 for D6S282 and 3.70 for D6S271, two markers on 6p21.1, as well as obtaining an indication of possible linkage for schizophrenia. Our sample comprised two large families in Denmark. Markers in the region that was implicated by the study of Arolt et al. [1996, 1999] were analyzed as part of a genome scan using the “latent trait (L.T.) model” for the co‐transmission of schizophrenia and ETD that we had previously fitted to segregation analysis data from Norway. We obtained a LOD score of 2.05 for D6S1017, a marker within 3 cM of the positive markers obtained by Arolt et al. [1996, 1999]. We regard our results as independent evidence supporting the findings of Arolt et al. [1996, 1999] and also as support for the L.T. model as a way of combining the traits ETD and schizophrenia. © 2004 Wiley‐Liss, Inc.
Association analysis of two candidate phospholipase genes that map to the chromosome 15q15.1‐15.3 region associated with reading disability
Authors: Morris D.W. , Ivanov D. , Robinson L. , Williams N. , Stevenson J. , Owen M.J. , Williams J. , O'Donovan M.C. 
Published: May 2004

AbstractMolecular genetic studies have suggested a reading disability (RD, dyslexia) susceptibility locus on chromosome 15q. We have previously mapped this locus by association to the region surrounding D15S994. Very little is known about the neurobiological processes involved in RD, and therefore selecting positional candidate genes for analysis based upon function is difficult. Nevertheless we were able to identify two functional candidates based upon existing hypotheses. Both were phospholipase genes, phospholipase C β 2 (PLCB2) and phospholipase A2, group IVB (cytosolic; PLA2G4B). D15S944 is located within PLCB2 and is 1.6 Mb from PLA2G4B. We examined each gene for association using a mixed direct and indirect association approach, a case (n = 164)/control (n = 174) sample, and a partially overlapping sample of 178 RD parent‐proband trios from South Wales and England. Mutation analysis revealed 14 sequence variants in PLCB2 and 33 variants in PLA2G4B. All non‐synonymous SNPs were genotyped as were SNPs across each gene with maximum distance between SNPs of 6 kb. Case‐control analyses revealed modest evidence (0.01 < P < 0.05) for association between a single variant in PLCB2 and two variants in PLA2G4B. However, association was not confirmed in the family based sample. As the latter sample has previously generated replicated significant evidence for association between RD and markers/haplotypes surrounding D15S944, it should have sufficient power to detect association to variants in susceptibility gene itself. We conclude that neither gene accounts for the association signal we previously observed. As these are the only clear cut functional candidate genes in the region, identification of the putative susceptibility locus for RD on 15q will require more methodical non‐hypothesis driven positional cloning approaches. © 2004 Wiley‐Liss, Inc.
Dermatoglyphic profile in 22q deletion syndrome
Authors: Martín B. , Fañanás L. , Gutiérrez B. , Chow E.W.C. , Bassett A.S. 
Published: May 2004

AbstractA genetic subtype of schizophrenia has been described in 22q11 Deletion syndrome. Previous studies have described an excess of dermatoglyphic alterations in schizophrenia, such as low a–b ridge counts (ABRCs), a high frequency of ridge dissociations, and increased dermatoglyphic fluctuating asymmetry. Little is known however, about the dermatoglyphic profile of 22qDS subjects showing psychotic symptoms and its similarity to the previously reported anomalies in schizophrenia. We studied the palmar dermatoglyphics of 22 subjects with 22qDS of predominantly Caucasian origin, 15 of whom had psychotic illness, and in 84 healthy controls of similar ethnicity. We observed higher values for total ATD angle in cases than in controls (P = 0.04). In addition, there was an excess of radial figures in the hypothenar area in cases, especially in the left hand. Interestingly, greater fluctuating asymmetry, determined by the absolute difference between right and left ABRC, was observed in 22qDS subjects compared to controls (P = 0.05). However, no differences were found for ABRCs and frequency of dissociations. Despite the small sample size, the palmprints analyzed suggest the existence of an altered dermatoglyphic profile in 22qDS, involving: (i) ATD angle amplitude, (ii) presence of radial loops in the hypothenar area, and (iii) an increment of fluctuating asymmetry. The first two features are similar to those found in other genetic syndromes associated with low IQ, while high levels of fluctuating asymmetry have often been reported in schizophrenia. © 2004 Wiley‐Liss, Inc.
Are phonological processing deficits part of the broad autism phenotype?
Authors: Bishop Dorothy V.M. , Maybery Murray , Wong Dana , Maley Alana , Hill Wayne , Hallmayer Joachim 
Published: May 2004

AbstractTwo tests of phonological processing, nonword repetition, and nonsense passage reading, were administered to 80 probands with autistic disorder or PDDNOS (index cases) and 59 typically developing controls, together with their parents and siblings. In addition, parents completed a questionnaire about history of language and literacy problems, and all participants were given tests of verbal (VIQ) and performance IQ (PIQ). Parents also completed the Autism‐Spectrum Quotient, which was used to index the broad autism phenotype. Index probands scored well below control probands on the two phonological tests. However, on neither phonological measure did index relatives differ from control relatives. Within the index group, there was no relationship between the proband's level of VIQ, or age at achieving phrase speech, and phonological score of relatives. VIQ was the only measure to show any familiality within the index group. Reported history of language and literacy problems did not differentiate index parents from control parents overall, but those who were categorized as cases of the broad phenotype reported more history of language and literacy problems than did other index parents. However, they did not have poorer scores on the phonological measures. It is concluded that phonological processing deficits are not part of the broad autism phenotype. © 2004 Wiley‐Liss, Inc.
Conformational basis for the biological activity of TOAC‐labeled angiotensin II and bradykinin: Electron paramagnetic resonance, circular dichroism, and fluorescence studies
Authors: Schreier Shirley , Barbosa Simone R. , Casallanovo Fábio , Vieira Renata de F. F. , Cilli Eduardo M. , Paiva Antonio C. M. , Nakaie Clóvis R. 
Published: May 2004

AbstractN‐Terminally and internally labeled analogues of the hormones angiotensin (AII, DRVYIHPF) and bradykinin (BK, RPPGFSPFR) were synthesized containing the paramagnetic amino acid 2,2,6,6‐tetramethylpiperidine‐1‐oxyl‐4‐amino‐4‐carboxylic acid (TOAC). TOAC replaced Asp1 (TOAC1‐AII) and Val3 (TOAC3‐AII) in AII and was inserted prior to Arg1 (TOAC0‐BK) and replacing Pro3 (TOAC3‐BK) in BK. The peptide conformational properties were examined as a function of trifluoroethanol (TFE) content and pH. Electron paramagnetic resonance spectra were sensitive to both variables and showed that internally labeled analogues yielded rotational correlation times (τC) considerably larger than N‐terminally labeled ones, evincing the greater freedom of motion of the N‐terminus. In TFE, τC increased due to viscosity effects. Calculation of τCpeptide/τCTOAC ratios indicated that the peptides acquired more folded conformations. Circular dichroism spectra showed that, except for TOAC1‐AII in TFE, the N‐terminally labeled analogues displayed a conformational behavior similar to that of the parent peptides. In contrast, under all conditions, the TOAC3 derivatives acquired more restricted conformations. Fluorescence spectra of AII and its derivatives were especially sensitive to the ionization of Tyr4. Fluorescence quenching by the nitroxide moiety was much more pronounced for TOAC3‐AII. The conformational behavior of the TOAC derivatives bears excellent correlation with their biological activity, since, while the N‐terminally labeled peptides were partially active, their internally labeled counterparts were inactive [Nakaie, C. R., et al., Peptides 2002, 23, 65–70]. The data demonstrate that insertion of TOAC in the middle of the peptide chain induces conformational restrictions that lead to loss of backbone flexibility, not allowing the peptides to acquire their receptor‐bound conformation. © 2004 Wiley Periodicals, Inc. Biopolymers, 2004
Ribosome motions modulate electrostatic properties
Authors: Trylska Joanna , Konecny Robert , Tama Florence , Brooks Charles L. , McCammon J. Andrew 
Published: May 2004

AbstractThe electrostatic properties of the 70S ribosome of Thermus thermophilus were studied qualitatively by solving the Poisson–Boltzmann (PB) equation in aqueous solution and with physiological ionic strength. The electrostatic potential was calculated for conformations of the ribosome derived by recent normal mode analysis (Tama, F., et al. Proc Natl Acad Sci USA 2003 100, 9319–9323) of the ratchet‐like reorganization that occurs during translocation (Frank, J.; Agrawal, R. K. Nature 2000 406, 318–322). To solve the PB equation, effective parameters (charges and radii), applicable to a highly charged backbone model of the ribosome, were developed. Regions of positive potential were found at the binding site of the elongation factors G and Tu, as well as where the release factors bind. Large positive potential areas are especially pronounced around the L11 and L6 proteins. The region around the L1 protein is also positively charged, supporting the idea that L1 may interact with the E‐site tRNA during its release from the ribosome after translocation. Functional rearrangement of the ribosome leads to electrostatic changes which may help the translocation of the tRNAs during the elongation stage. © 2004 Wiley Periodicals, Inc. Biopolymers, 2004
One‐step analysis of testis steroidogenesis from neonatal exposure to synthetic estrogen by normal‐phase HPLC
Authors: Kuwada Masahiro , Kawashima Rei , Furudate Senich , Sugano Sachiko , Maki Jun 
Published: May 2004

AbstractNeonatal exposure to synthetic estrogen endocrine disruptors or estrogen‐receptor inhibitors induces developmental abnormalities in the male reproductive system. To investigate whether neonatal exposure affects spermatogenesis in juvenile and pubertal testis, Sprague–Dawley rat pups were given synthetic estrogen endocrine disruptors or estrogen‐receptor inhibitors by a single injection on the day of birth at concentrations ranging between 2 to 40 mm, and sacriﬁced on day 21 (juvenile), 35 (prepuberty) or 50 (puberty). The testes were weighed and examined histologically at each stage. Further, the metabolites of steroidogenesis were analyzed using normal‐phase high performance liquid chromatography. Neonatal exposure signiﬁcantly reduced testis weights and steroidogenesis to one‐ﬁfth to one‐half of that of the juvenile control, and further suppressed irreversible steroidogenesis and spermatogenesis during puberty. Copyright © 2004 John Wiley & Sons, Ltd.
Encapsulation of isohexenylnaphthazarins in cyclodextrins
Authors: Assimopoulou A. N. , Papageorgiou V. P. 
Published: May 2004

AbstractNaturally occurring isohexenylnaphthazarins (IHN), such as Alkannin, Shikonin (A/S) and their derivatives, are potent pharmaceutical substances with a wide spectrum of biological activity. In the present study, inclusion complexes of alkannin and shikonin commercial samples and IHN derivatives in the form of an oily extract of Alkanna tinctoria roots were formed with β‐cyclodextrin (CD) and β‐HPCD. These complexes were investigated to evaluate the effect of complexation on their aqueous solubility, decoloration, and also the percentage of polymeric A/S and IHN derivatives enclosed in the CDs cavity, since these decrease the active monomeric IHN. Both β‐CD and β‐HPCD increased the aqueous solubility of A/S and IHN derivatives and thus inclusion complexes can be used as drug delivery systems for A/S in both internal (capsules, tablets) and external hydrophilic pharmaceutical and cosmetic preparations (creams, gels, sprays) with enhanced bioavailability. The inclusion complexes formed had a pale purple colour, contributing to the partial decoloration of the A/S and thus of the ﬁnal pharmaceutical preparations. Finally, CDs selectively included more monomeric and less polymeric IHN, compared with the initial each time sample that is encapsulated; thus inclusion complexes may present enhanced biological activity. Copyright © 2004 John Wiley & Sons, Ltd.
Simultaneous determination of chlorpheniramine and pseudoephedrine in human plasma by liquid chromatography–tandem mass spectrometry
Authors: Chen Xiaoyan , Zhang Yong , Zhong Dafang 
Published: May 2004

AbstractA sensitive and speciﬁc procedure for simultaneous quantitation of chlorpheniramine and pseudoephedrine in human plasma has been developed and validated. Analytes were extracted from plasma samples by liquid–liquid extraction, separated on a Diamonsil C18 column (250 × 4.6 mm i.d.) and detected by tandem mass spectrometry with an atmospheric pressure chemical ionization interface. Diphenhydramine was used as the internal standard. The method has a lower limit of quantitation of 0.2 and 2.0 ng/mL for chlorpheniramine and pseudoephedrine, respectively. The intra‐ and inter‐day relative standard deviation, calculated from quality control (QC) samples were below 4.3% for chlorpheniramine and below 9.5% for pseudoephedrine. The inter‐day relative error as determined from QC samples was within 4.7% for each analyte. The overall extraction recoveries of chlorpheniramine and pseudoephedrine were 77 and 61% on average, respectively. The method was successfully applied to pharmaockinetic study of chlorpheniramine and pseudoephedrine in volunteers receiving formulations containing 4 mg of chlorpheniramine maleate and 60 mg of pseudoephedrine hydrochloride. Copyright © 2004 John Wiley & Sons, Ltd.
The Hummel–Dreyer method: impact in pharmacology
Authors: Šoltés Ladislav 
Published: May 2004

AbstractReviews devoted to drug–protein binding present mostly a variety of analytical methods applied to studying the unique process when the protein reversibly binds a low‐molecular‐weight substance—the drug. This report, however, reviews the great majority of papers presenting the application of one particular method introduced by Hummel and Dreyer in 1962: Measurement of protein‐binding phenomena by gel ﬁltration. The main criterion in reviewing published papers was the application of the Hummel–Dreyer method when the counterpart substances were the drug and the human plasma protein. Copyright © 2003 John Wiley & Sons, Ltd.
Investigation into the use of C‐ and N‐terminal GFP fusion proteins for subcellular localization studies using reverse transfection microarrays
Authors: Palmer Ella , Freeman Tom 
Published: May 2004

AbstractReverse transfection microarrays were described recently as a high throughput method for studying gene function. We have investigated the use of this technology for determining the subcellular localization of proteins. Genes encoding 16 proteins with a variety of functions were placed in Gateway expression constructs with 3′ or 5′ green fluorescent protein (GFP) tags. These were then packaged in transfection reagent and spotted robotically onto a glass slide to form a reverse transfection array. HEK293T cells were grown over the surface of the array until confluent and GFP fluorescence visualized by confocal microscopy. All C‐terminal fusion proteins localized to cellular compartments in accordance with previous studies and/or bioinformatic predictions. However, less than half of the N‐terminal fusion proteins localized correctly. Of those that were not in concordance with the C‐terminal tagged proteins, half did not exhibit expression and the remainder had differing subcellular localizations to the C‐terminal fusion protein. This data indicates that N‐terminal tagging with GFP adversely affects the protein localization in reverse transfection assays, whereas tagging with GFP at the C‐terminal is generally better in preserving the localization of the native protein. We discuss these results in the context of developing high‐throughput subcellular localization assays based on the reverse transfection array technology. Copyright © 2004 John Wiley & Sons, Ltd.
Mapping the Gene Ontology into the Unified Medical Language System
Authors: Lomax Jane , McCray Alexa T. 
Published: May 2004

AbstractWe have recently mapped the Gene Ontology (GO), developed by the Gene Ontology Consortium, into the National Library of Medicine's Unified Medical Language System (UMLS). GO has been developed for the purpose of annotating gene products in genome databases, and the UMLS has been developed as a framework for integrating large numbers of disparate terminologies, primarily for the purpose of providing better access to biomedical information sources. The mapping of GO to UMLS highlighted issues in both terminology systems. After some initial explorations and discussions between the UMLS and GO teams, the GO was integrated with the UMLS. Overall, a total of 23% of the GO terms either matched directly (3%) or linked (20%) to existing UMLS concepts. All GO terms now have a corresponding, official UMLS concept, and the entire vocabulary is available through the web‐based UMLS Knowledge Source Server. The mapping of the Gene Ontology, with its focus on structures, processes and functions at the molecular level, to the existing broad coverage UMLS should contribute to linking the language and practices of clinical medicine to the language and practices of genomics. Copyright © 2004 John Wiley & Sons, Ltd.
Design, implementation and maintenance of a model organism database for Arabidopsis thaliana
Authors: Weems Danforth , Miller Neil , Garcia‐Hernandez Margarita , Huala Eva , Rhee Seung Y. 
Published: May 2004

AbstractThe Arabidopsis Information Resource (TAIR) is a web‐based community database for the model plant Arabidopsis thaliana. It provides an integrated view of genes, sequences, proteins, germplasms, clones, metabolic pathways, gene expression, ecotypes, polymorphisms, publications, maps and community information. TAIR is developed and maintained by collaboration between software developers and biologists. Biologists provide specification and use cases for the system, acquire, analyse and curate data, interact with users and test the software. Software developers design, implement and test the database and software. In this review, we briefly describe how TAIR was built and is being maintained. Copyright © 2004 John Wiley & Sons, Ltd.
Comparative genomic assessment of novel broad‐spectrum targets for antibacterial drugs
Authors: White Thomas A. , Kell Douglas B. 
Published: May 2004

AbstractSingle and multiple resistance to antibacterial drugs currently in use is spreading, since they act against only a very small number of molecular targets; finding novel targets for anti‐infectives is therefore of great importance. All protein sequences from three pathogens (Staphylococcus aureus, Mycobacterium tuberculosis and Escherichia coli O157:H7 EDL993) were assessed via comparative genomics methods for their suitability as antibacterial targets according to a number of criteria, including the essentiality of the protein, its level of sequence conservation, and its distribution in pathogens, bacteria and eukaryotes (especially humans). Each protein was scored and ranked based on weighted variants of these criteria in order to prioritize proteins as potential novel broad‐spectrum targets for antibacterial drugs. A number of proteins proved to score highly in all three species and were robust to variations in the scoring system used. Sensitivity analysis indicated the quantitative contribution of each metric to the overall score. After further analysis of these targets, tRNA methyltransferase (trmD) and translation initiation factor IF‐1 (infA) emerged as potential and novel antimicrobial targets very worthy of further investigation. The scoring strategy used might be of value in other areas of post‐genomic drug discovery. Copyright © 2004 John Wiley & Sons, Ltd.
Chiral investigation of midodrine, a long‐acting α‐adrenergic stimulating agent
Authors: Quaglia M.G. , Farina A. , Palmery M. , Desideri N. , Donati E. , Bossù E. , Strano S. 
Published: May 2004

AbstractMidodrine hydrochloride is a peripheral α1‐adrenoreceptor agonist that induces venous and arterial vasoconstriction. Midodrine, after oral or intravenous administration, undergoes enzymatic hydrolysis and releases deglymidodrine, a pharmacologically active metabolite. Midodrine and deglymidodrine have a chiral carbon in the 2‐position. To investigate the bioactivity of racemates and enantiomers of the drug and metabolite, three chromatographic chiral stationary phases, Chiralcel OD‐H, Chiralcel OD‐R, and α1‐AGP, were evaluated for enantiomeric resolution. Good enantioseparation of midodrine racemate was obtained using the Chiralcel OD‐H column. This stationary phase was then used to collect separately the midodrine enantiomers. By alkaline hydrolysis of rac‐midodrine and each separated enantiomer, rac‐deglymidodrine and its enantiomers were prepared. The control of the enantiomeric purity was carried out by α1‐AGP stationary phase, while the hydrolysis of rac‐midodrine and its enantiomers was controlled by capillary electrophoresis using trimethyl‐β‐cyclodextrin as chiral selector. The pharmacological activity of the two racemates and the two enantiomeric pairs was tested in vitro on a strip of rabbit descending thoracic aorta. The tests continued that the activity of the drug and metabolite is due only to the (−)‐enantiomer because neither of the (+)‐enantiomers is active. Chirality 16:356–362, 2004. ©2004 Wiley‐Liss, Inc.