bluuebunny/crossref_metadata_2025_split huggingface dataset:
Parliamentary Representation in Europe: Past, Present, and Future
Authors: Gabel Matthew 
Published: November 2002

Richard Katz and Bernhard Wessels, eds., The European Parliament, the National Parliaments, and European Integration (New York: Oxford University Press, 1999), 280pp., £35, h.b., ISBN 0-19-829660-6.Heinrich Best and Maurizio Cotta, eds., Parliamentary Representatives in Europe, 1848–2000 (Oxford and New York: Oxford University Press 2000), 530pp., £55, h.b., ISBN 0-19-829793-9.Jean Blondel, Richard Sinnott and Palle Svensson, People and Parliament in the European Union. Participation, Democracy, and Legitimacy (Oxford: Clarendon Press, 1998), 287pp., £45, h.b., ISBN 0-19-829308-9.Amie Kreppel, The European Parliament and Supranational Party System. A Study in Institutional Development (Cambridge: Cambridge University Press, 2001), 288pp., £40, h.b., ISBN 0-521-80625-9.
Historical Representations of Yaʿqūb b. al-Layth: A Reappraisal
Authors: Tor D. G. 
Published: November 2002

AbstractThe extraordinary ascendancy of the Saffarid dynasty began with the meteoric career of its founder, Yaʿqūb b. al-Layth al-Saffār. Yaʿqūb appeared on the historical scene in 238/852 as the member of an Eastern Iranian military band, and ended his days as the ruler over a vast swathe of territory stretching from today's ʿIraq to the borders of today's India; while at least theoretical acknowledgement of his overlordship was found both in Central Asia and the holy cities of Arabia.
The 1934 Chinese Mission to Tibet: A Re-examination
Authors: Lin Hsiao-Ting 
Published: November 2002

AbstractIn the spring of 1934, a Chinese mission led by General Huang Musong, then Deputy Chief of the General Staff of the Guomindang regime, was dispatched to Lhasa with the official purpose of offering condolences to the late 13th Dalai Lama who died in late 1933. Huang's visit to Tibet undoubtedly was the most politically symbolic event in Sino-Tibetan relations since the collapse of the Qing dynasty. He became the most high-profile of Chinese officials to have entered Lhasa since 1911, when the Chinese Republic was created. Before returning to Nanking, Huang left a representative office, along with a wireless set in Lhasa; these could be actions which the Chinese considered marked their authority in Tibet.
Novel PAX6 Binding Sites in the Human Genome and the Role of Repetitive Elements in the Evolution of Gene Regulation
Authors: Zhou Yi-Hong , Zheng Jessica B. , Gu Xun , Saunders Grady F. , Yung W.-K. Alfred 
Published: November 2002

Pax6 is a critical transcription factor in the development of the eye, pancreas, and central nervous system. It is composed of two DNA-binding domains, the paired domain (PD), which has two helix–turn–helix (HTH) motifs, and the homeodomain (HD), made up from another HTH motif. Each HTH motif can bind to DNA separately or in combination with the others. We identified three novel binding sites that are specific for the PD and HD domains of human PAX6 from single-copy human genomic DNA libraries using cyclic amplification of protein binding sequences (CAPBS) and electrophoretic mobility shift assays (EMSAs). One of the binding sites was found within sequences of repetitive Alu elements. However, most of the Alu sequences were unable to bind to PAX6 because of a small number of mismatches (mostly in CpG dinucleotide hot spots) in the consensus Alu sequences. PAX6 binding Alu elements are found primarily in old and intermediate-aged Alu subfamilies. These data along with our previously identified B1-type Pax6 binding site showed that evolutionarily conserved Pax6 has target sites that are disparate in primates and rodents. This difference indicates that human and mouse Pax6-regulated gene networks may have evolved through these lineage-specific repeat elements.[The sequence data from this study have been submitted to GenBank under accession no. AF451322. The following individual kindly provided reagents, samples, or unpublished information as indicated in this paper: L. Yu.]
SNPSTRs: Empirically Derived, Rapidly Typed, Autosomal Haplotypes for Inference of Population History and Mutational Processes
Authors: Mountain Joanna L. , Knight Alec , Jobin Matthew , Gignoux Christopher , Miller Adam , Lin Alice A. , Underhill Peter A. 
Published: November 2002

Each independently evolving segment of the genomes of a sexually reproducing organism has a separate history reflecting part of the evolutionary history of that organism. Uniparentally or clonally inherited DNA segments such as the mitochondrial and chloroplast genomes and the nonrecombining portion of the Y chromosome have provided, to date, most of the known data regarding compound haplotypic variation within and among populations. These comparatively small segments include numerous polymorphic sites and undergo little or no recombination. Recombining autosomes, however, comprise the major repository of genetic variation. Technical challenges and recombination have limited large-scale application of autosomal haplotypes. We have overcome this barrier through development of a general approach to the assessment of short autosomal DNA segments. Each such segment includes one or more single nucleotide polymorphisms (SNPs) and exactly one short tandem repeat (STR) locus. With dramatically different mutation rates, these two types of genetic markers provide complementary evolutionary information. We call the combination of a SNP and a STR polymorphism a SNPSTR, and have developed a simple, rapid method for empirically determining gametic phase for double and triple heterozygotes. Here, we illustrate the approach with two SNPSTR systems. Although even one system provides insight into population history, the power of the approach lies in combining results from multiple SNPSTR systems.[Supplemental material is available online at http://www.genome.org. The following individual kindly provided reagents, samples, or unpublished information as indicated in this paper: L. Luca Cavelli-Sforza.]
Genomic Signature Tags (GSTs): A System for Profiling Genomic DNA
Authors: Dunn John J. , McCorkle Sean R. , Praissman Laura A. , Hind Geoffrey , van der Lelie Daniel , Bahou Wadie F. , Gnatenko Dmitri V. , Krause Maureen K. 
Published: November 2002

Genomic signature tags (GSTs) are the products of a method we have developed for identifying and quantitatively analyzing genomic DNAs. The DNA is initially fragmented with a type II restriction enzyme. An oligonucleotide adaptor containing a recognition site forMmeI, a type IIS restriction enzyme, is then used to release 21-bp tags from fixed positions in the DNA relative to the sites recognized by the fragmenting enzyme. These tags are PCR-amplified, purified, concatenated, and then cloned and sequenced. The tag sequences and abundances are used to create a high-resolution GST sequence profile of the genomic DNA. GSTs are shown to be long enough for use as oligonucleotide primers to amplify adjacent segments of the DNA, which can then be sequenced to provide additional nucleotide information or used as probes to identify specific clones in metagenomic libraries. GST analysis of the 4.7-Mb Yersinia pestis EV766 genome using BamHI as the fragmenting enzyme and NlaIII as the tagging enzyme validated the precision of our approach. The GST profile predicts that this strain has several changes relative to the archetype CO92 strain, including deletion of a 57-kb region of the chromosome known to be an unstable pathogenicity island.[The following individuals kindly provided reagents, samples, or unpublished information as indicated in the paper: W. Crockett, K. Pellechi, J. Paparelli, J. Romeo, and K. Thompson.]
Segmental Polymorphisms in the Proterminal Regions of a Subset of Human Chromosomes
Authors: Der-Sarkissian Hera , Vergnaud Gilles , Borde Yves-Marie , Thomas Gilles , Londoño-Vallejo José-Arturo 
Published: November 2002

The subtelomeric domains of chromosomes are probably the most rapidly evolving structures of the human genome. The highly variable distribution of large duplicated subtelomeric segments has indicated that frequent exchanges between nonhomologous chromosomes may have been taking place during recent genome evolution. We have studied the extent and variability of such duplications using in situ hybridization techniques and a set of well-defined subtelomeric cosmid probes that identify discrete regions within the subtelomeric domain. In addition to reciprocal translocation and illegitimate recombination events that could explain the observed mosaic pattern of subtelomeric regions, it is likely that homology-based recombination mechanisms have also contributed to the spread of distal subtelomeric sequences among particular groups of nonhomologous chromosome arms. The frequency and distribution of large-scale subtelomeric polymorphisms may have direct implications for the design of chromosome-specific probes that are aimed at the identification of cryptic subtelomeric deletions. Furthermore, our results indicate that the relevance of some of the telomere closures proposed within the present Human Genome Sequence draft are restricted to specific allelic variants of unknown frequencies.[The sequence of cosmid ICRF10 (carrying DNF92) was deposited in GenBank under accession no. Y13543.]
Genomic Structure and Evolution of the Ancestral Chromosome Fusion Site in 2q13–2q14.1 and Paralogous Regions on Other Human Chromosomes
Authors: Fan Yuxin , Linardopoulou Elena , Friedman Cynthia , Williams Eleanor , Trask Barbara J. 
Published: November 2002

Human chromosome 2 was formed by the head-to-head fusion of two ancestral chromosomes that remained separate in other primates. Sequences that once resided near the ends of the ancestral chromosomes are now interstitially located in 2q13–2q14.1. Portions of these sequences had duplicated to other locations prior to the fusion. Here we present analyses of the genomic structure and evolutionary history of >600 kb surrounding the fusion site and closely related sequences on other human chromosomes. Sequence blocks that closely flank the inverted arrays of degenerate telomere repeats marking the fusion site are duplicated at many, primarily subtelomeric, locations. In addition, large portions of a 168-kb centromere-proximal block are duplicated at 9pter, 9p11.2, and 9q13, with 98%–99% average sequence identity. A 67-kb block on the distal side of the fusion site is highly homologous to sequences at 22qter. A third ∼100-kb segment is 96% identical to a region in 2q11.2. By integrating data on the extent and similarity of these paralogous blocks, including the presence of phylogenetically informative repetitive elements, with observations of their chromosomal distribution in nonhuman primates, we infer the order of the duplications that led to their current arrangement. Several of these duplicated blocks may be associated with breakpoints of inversions that occurred during primate evolution and of recurrent chromosome rearrangements in humans.[Supplemental material is available online at http://www.genome.org. The following individuals kindly provided reagents, samples, or unpublished information as indicated in the paper: T. Newman, C. Harris, and J. Young.]
Gene Content and Function of the Ancestral Chromosome Fusion Site in Human Chromosome 2q13–2q14.1 and Paralogous Regions
Authors: Fan Yuxin , Newman Tera , Linardopoulou Elena , Trask Barbara J. 
Published: November 2002

Various portions of the region surrounding the site where two ancestral chromosomes fused to form human chromosome 2 are duplicated elsewhere in the human genome, primarily in subtelomeric and pericentromeric locations. At least 24 potentially functional genes and 16 pseudogenes reside in the 614-kb of sequence surrounding the fusion site and paralogous segments on other chromosomes. By comparing the sequences of genomic copies and transcripts, we show that at least 18 of the genes in these paralogous regions are transcriptionally active. Among these genes are new members of the cobalamin synthetase W domain (CBWD) and forkhead domain FOXD4 gene families. Copies of RPL23A and SNRPA1 on chromosome 2 are retrotransposed-processed pseudogenes that were included in segmental duplications; we find 53 RPL23A pseudogenes in the human genome and map the functional copy of SNRPA1 to 15qter. The draft sequence of the human genome also provides new information on the location and intron–exon structure of functional copies of other 2q-fusion genes (PGM5, retina-specific F379, helicaseCHLR1, and acrosin). This study illustrates that the duplication and rearrangement of subtelomeric and pericentromeric regions have functional relevance to human biology; these processes can change gene dosage and/or generate genes with new functions.[Supplemental material is available online athttp://www.genome.org. Sequence data reported in this paper have been deposited in GenBank and assigned the following accession nos.:AF452722, AF452723, and AF452724.]
Gene Expression Analysis Using Oligonucleotide Arrays Produced by Maskless Photolithography
Authors: Nuwaysir Emile F. , Huang Wei , Albert Thomas J. , Singh Jaz , Nuwaysir Kate , Pitas Alan , Richmond Todd , Gorski Tom , Berg James P. , Ballin Jeff , McCormick Mark , Norton Jason , Pollock Tim , Sumwalt Terry , Butcher Lawrence , Porter DeAnn , Molla Michael , Hall Christine , Blattner Fred , Sussman Michael R. , Wallace Rodney L. , Cerrina Franco , Green Roland D. 
Published: November 2002

Microarrays containing 195,000 in situ synthesized oligonucleotide features have been created using a benchtop, maskless photolithographic instrument. This instrument, the Maskless Array Synthesizer (MAS), uses a digital light processor (DLP) developed by Texas Instruments. The DLP creates the patterns of UV light used in the light-directed synthesis of oligonucleotides. This digital mask eliminates the need for expensive and time-consuming chromium masks. In this report, we describe experiments in which we tested this maskless technology for DNA synthesis on glass surfaces. Parameters examined included deprotection rates, repetitive yields, and oligonucleotide length. Custom gene expression arrays were manufactured and hybridized toDrosophila melanogasterand mouse samples. Quantitative PCR was used to validate the gene expression data from the mouse arrays.[The sequence data from this study have been submitted to GEO under accession nos. GPL208, GSM2409, GSM2410, GSM2411, GSM2412, GSM2413, GSM2414, GSE81, GSE82.]
Signatures of Domain Shuffling in the Human Genome
Authors: Kaessmann Henrik , Zöllner Sebastian , Nekrutenko Anton , Li Wen-Hsiung 
Published: November 2002

To elucidate the role of exon shuffling in shaping the complexity of the human genome/proteome, we have systematically analyzed intron phase distributions in the coding sequence of human protein domains. We found that introns at the boundaries of domains show high excess of symmetrical phase combinations (i.e., 0–0, 1–1, and 2–2), whereas nonboundary introns show no excess symmetry. This suggests that exon shuffling has primarily involved rearrangement of structural and functional domains as a whole. Furthermore, we found that domains flanked by phase 1 introns have dramatically expanded in the human genome due to domain shuffling and that 1–1 symmetrical domains and domain families are nonrandomly distributed with respect to their age. The predominance and extracellular location of 1–1 symmetrical domains among domains specific to metazoans suggests that they are associated with the rise of multicellularity. On the other hand, 0–0 symmetrical domains tend to be over-represented among ancient protein domains that are shared between the eukaryotic and prokaryotic kingdoms, which is compatible with the suggestion of primordial domain shuffling in the progenote. To see whether the human data reflect general genomic patterns of metazoans, similar analyses were done for the nematodeCaenorhabditis elegans. Although the C. elegans data generally concur with the human patterns, we identified fewer intron-bounded domains in this organism, consistent with the lower complexity of C. elegans genes.[The following individuals kindly provided reagents, samples, or unpublished information as indicated in the paper: Z. Gu and R. Stevens.]
Early Gene Expression Associated with the Commitment and Differentiation of a Plant Tracheary Element Is Revealed by cDNA–Amplified Fragment Length Polymorphism Analysis[W]
Authors: Milioni Dimitra , Sado Pierre-Etienne , Stacey Nicola J. , Roberts Keith , McCann Maureen C. 
Published: November 2002

AbstractIsolated mesophyll cells from Zinnia elegans are induced by auxin and cytokinin to form tracheary elements (TEs) in vitro with high synchrony. To reveal the changing patterns of gene expression during the 48 h of transdifferentiation from meso-phyll to TE cell fate, we used a cDNA–amplified fragment length polymorphism approach to generate expression profiles of &gt;30,000 cDNA fragments. Transcriptional changes of 652 cDNA fragments were observed, of which 304 have no previously described function or sequence identity. Sixty-eight genes were upregulated within 30 min of induction and represent key candidates for the processes that underlie the early stages of commitment and differentiation to a TE cell fate.
TheChlamydomonas reinhardtiiPlastid Chromosome
Authors: Maul Jude E. , Lilly Jason W. , Cui Liying , dePamphilis Claude W. , Miller Webb , Harris Elizabeth H. , Stern David B. 
Published: November 2002

AbstractChlamydomonas reinhardtii is a unicellular eukaryotic alga possessing a single chloroplast that is widely used as a model system for the study of photosynthetic processes. This report analyzes the surprising structural and evolutionary features of the completely sequenced 203,395-bp plastid chromosome. The genome is divided by 21.2-kb inverted repeats into two single-copy regions of ∼80 kb and contains only 99 genes, including a full complement of tRNAs and atypical genes encoding the RNA polymerase. A remarkable feature is that &gt;20% of the genome is repetitive DNA: the majority of intergenic regions consist of numerous classes of short dispersed repeats (SDRs), which may have structural or evolutionary significance. Among other sequenced chlorophyte plastid genomes, only that of the green alga Chlorella vulgaris appears to share this feature. The program MultiPipMaker was used to compare the genic complement of Chlamydomonas with those of other chloroplast genomes and to scan the genomes for sequence similarities and repetitive DNAs. Among the results was evidence that the SDRs were not derived from extant coding sequences, although some SDRs may have arisen from other genomic fragments. Phylogenetic reconstruction of changes in plastid genome content revealed that an accelerated rate of gene loss also characterized the Chlamydomonas/Chlorella lineage, a phenomenon that might be independent of the proliferation of SDRs. Together, our results reveal a dynamic and unusual plastid genome whose existence in a model organism will allow its features to be tested functionally.
Dynamic Confocal Imaging of Living Brain
Authors: Paton Julian F. R. , Kasparov Sergey 
Published: November 2002

IntroductionThis special issue contains an exciting series of papers that are based on presentations made at a workshop entitled ‘Dynamic Confocal Imaging of Living Brain’ which was held on the 30th June 2001 at the University of Bristol. The paper by Howell et al. was not presented at this symposium but is included to further portray the versatility of confocal imaging.As the saying goes: ‘Seeing is believing’ and in this day and age imaging of the brain has become an important modern research tool. With the recent technological advances in single and multi‐photon microscopy, structures beneath the surface of the brain can be imaged with sub‐micrometre resolution to further enhance our understanding of inter‐ and intra‐cellular signalling. With the development and employment of calcium indicators and naturally occurring fluorescent proteins the field has advanced dramatically into imaging of living processes. The following papers encapsulate the types of research that can now be performed with confocal microscopes for imaging dynamic events in living brain both in vitro and in vivo.We are grateful to the Physiological Society, Leica Microsystems and Molecular Probes for their financial support.
Influence of nonspecific brain and plasma binding on CNS exposure: implications for rational drug discovery
Authors: Cory Kalvass J. , Maurer Tristan S. 
Published: November 2002

AbstractRelative plasma, brain and cerebrospinal fluid (CSF) exposures and unbound fractions in plasma and brain were examined for 18 proprietary compounds in rats. The relationship between in vivo brain‐to‐plasma ratio and in vitro plasma‐to‐brain unbound fraction (fu) was examined. In addition, plasma fu and brain fu were examined for their relationship to in vivo CSF‐to‐plasma and CSF‐to‐brain ratios, respectively. Findings were delineated based on the presence or absence of active efflux. Finally, the same comparisons were examined in FVB vs. MDR 1a/1b knockout mice for a selected P‐glycoprotein (Pgp) substrate. For the nine compounds without indications of active efflux, predictive correlations were observed between ratios of brain‐to‐plasma exposure and plasma‐to‐brain fu (r2 = 0.98), CSF‐to‐brain exposure vs. brain fu (r2 = 0.72), and CSF‐to‐plasma exposure vs. plasma fu (r2 = 0.82). For the nine compounds with indications of active efflux, nonspecific binding data tended to over predict the brain‐to‐plasma and CSF‐to‐plasma exposure ratios. Interestingly, CSF‐to‐brain exposure ratio was consistently under predicted by brain fu for this set. Using a select Pgp substrate, it was demonstrated that the brain‐to‐plasma exposure ratio was identical to that predicted by plasma‐to‐brain fu ratio in MDR 1a/1b knockout mice. In FVB mice, plasma‐to‐brain fu over predicted brain‐to‐plasma exposure ratio to the same degree as the difference in brain‐to‐plasma exposure ratio between MDR 1a/1b and FVB mice. Consistent results were obtained in rats, suggesting a similar kinetic behavior between species. These data illustrate how an understanding of relative tissue binding (plasma, brain) can allow for a quantitative examination of active processes that determine CNS exposure. The general applicability of this approach offers advantages over species‐ and mechanism‐specific approaches. Copyright © 2002 John Wiley & Sons, Ltd.
Pharmacokinetics of SB‐247083, a potent and selective endothelinA receptor antagonist, in the rat, dog, and monkey
Authors: Ward Keith W. , Azzarano Leonard M. , Morgan Jayme A. , Gould Michael J. , Perng Cherng‐Yih , Souder Pamela R. , Lundberg David , Smith Brian R. 
Published: November 2002

AbstractThe endothelins (ET) are among the most potent vasoconstrictors identified to date, and have been implicated in such diseases as renal failure, pulmonary hypertension, atherosclerosis, and congestive heart failure. There is currently interest in developing selective antagonists of the ET‐A subtype receptor, and one such antagonist is SB‐247083 ((E)‐[1‐butyl‐5‐[2‐(2‐carboxyphenyl) methoxy‐4‐chlorophenyl]‐1H‐pyrazole‐4‐yl]‐2‐[5‐methoxydihydrobenzofuran‐6‐yl]methyl]‐2‐propionic acid). This investigation was conducted to evaluate the preclinical pharmacokinetics of SB‐247083. Clearance of SB‐247083 was low to moderate in the rat and monkey, and high in the dog. Oral bioavailability of SB‐247083 administered as a solid formulation of the free acid was 24% in the rat, but low in the dog (4%) and the monkey (2%). An extensive in vitro salt form and formulation screen resulted in the identification of a formulation containing the monoarginyl salt with improved dissolution properties. This formulation provided a 2‐ to 4‐fold increase in oral bioavailability in each of the preclinical species. In the dog, this improvement was reversed by the pre‐administration of 0.1 N HCl to normalize the achlorhydric fasting dog stomach. These data show that SB‐247083 may have suitable drug properties for progression in development. Copyright © 2002 John Wiley & Sons, Ltd.