bluuebunny/crossref_metadata_2025 huggingface dataset:
“HARMLESS PLEASURE”: GENDER, SUSPENSE, AND JANE EYRE
Authors: Levine Caroline
Published: July 2002

“[I]T IS TIME THE OBSCURITY . . . WAS done away,” writes Charlotte Brontë in 1850. “The little mystery, which formerly yielded some harmless pleasure, has lost its interest. Circumstances have changed” (“Biographical Notice” 134). The “little mystery” she coyly invokes here was not so trivial in the eyes of the literary world. From the moment that Jane Eyre appeared, reviewers speculated wildly about the identity of the authors of Jane Eyre, Wuthering Heights, and The Tenant of Wildfell Hall. “[T]he whole reading-world of London was in a ferment to discover the unknown author,” writes Elizabeth Gaskell (271). When the identities of the three sisters emerged, it was something of a shock to most of the London literati to discover that the writers of these “coarse” and “repulsive” novels were young, sheltered Yorkshire women, daughters of a curate, who had seen little of the world.1 Although the secret had been slowly coming out, bit by bit, it was in 1850 that Charlotte Brontë put the speculations to rest with her “Biographical Notice of Ellis and Acton Bell,” written for a new edition of Wuthering Heights.
Application of a weather stress index for alerting the public to stressful weather in Hong Kong
Authors: Li P W , Chan S T
Published: July 2002

An operational procedure for alerting the public of stressful weather (exceptionally hot and cold situations) in Hong Kong has been implemented since late 1997. From a 28‐year (1968–1995) climatological database, criteria based on a weather stress index (WSI) was established to define stressful weather conditions. A special bulletin is issued to the public when exceptionally high (hot, i.e. ≥97.5%) or low (cold, i.e. ≤2.5%) WSI is forecast. The bulletin provides information on current or predicted stressful weather conditions as well as statements on precautionary action to take. A study was also carried out to examine the effects of WSI on mortality rates on days with extreme WSI. Preliminary results indicate that there was a relationship between low WSI and mortality rates in winter. In summer, however, the results were not conclusive. Copyright © 2000 Royal Meteorological Society
A review of ensemble forecasting techniques with a focus on tropical cyclone forecasting
Authors: Cheung Kevin K W
Published: July 2002

This paper presents a general review of ensemble forecasting techniques, with a focus on short‐range and tropical cyclone predictions. The basic ideas and terminology of ensemble forecasting are introduced, and using four measures to evaluate an ensemble (ensemble mean forecast, consistency, spread versus skill, and inclusiveness), various potential utilities (e.g. dynamical probabilistic forecasts) are illustrated. Since the perturbation methodologies designed for medium‐range forecasts of mid‐latitude synoptic‐scale systems –singular vectors, bred modes, and so on –are already quite mature, they are only briefly described here. The general problems encountered in applying ensemble forecasting techniques to short‐range and tropical cyclone forecasts are diagnosed, and some recent studies on these topics reviewed. In general, the perturbation methodologies used for short‐range ensembles to date can have a skill comparable to or slightly higher than their corresponding high‐resolution control forecast. However, the complicated problem of the relationship between initial condition errors and model deficiencies persists. A similar situation also applies to ensembles designed for tropical cyclone forecasting. An additional difficulty is the different error characteristics encountered in the tropics, mainly the result of the strong convection in the area and the mutual interaction with the ocean. Studies from several research groups use quite different perturbation methodologies, but the results are encouraging. Most of them performed ensemble forecasting of tropical cyclone motion, but extensions to tropical cyclone intensity forecasts are also being developed. Copyright © 2001 Royal Meteorological Society
A technique for consistent alteration of NWP output fields
Authors: Carroll E B
Published: July 2002

A workstation‐based NWP scheme is described which allows forecasters to reposition and change in intensity features such as fronts and depressions, and thus alter model fields in a realistic way. The technique is based on distortion of either geopotential height or potential vorticity (PV). In the latter case, the PV is calculated from geopotential distribution, distorted, then inverted to yield a modified, yet consistent and dynamically balanced, set of grid‐point data. Copyright © 1997 Royal Meteorological Society
SPECIFICITY OF COGNITIVE BIASES IN SOCIAL PHOBIA AND THEIR ROLE IN RECOVERY
Authors: McManus Freda , Clark David M. , Hackmann Ann
Published: July 2002

Cognitive theorists propose that each anxiety disorder is associated with a specific tendency to overestimate the danger inherent in particular situations or internal states. Studies comparing anxious patients with non-patient controls have shown that several anxiety disorders are associated with elevated subjective estimates of the likelihood (probability) and cost of negative events. The present study focuses on social phobia and extends previous findings by: a) including a control group of equally anxious patients with another anxiety disorder and b) investigating the effects of successful cognitive and drug treatments on patients' probability and cost estimates. In line with cognitive theory, the results indicate that social phobia is associated with a specific elevation in subjective estimates of both the probability and cost of potentially negative social events. Reductions in overestimation occurred in successful cognitive and drug treatment and were closely related to the degree of symptomatic improvement in both treatments. Contrary to previous findings, there was no evidence that reductions in cost were more important than reductions in probability.
Detecting malingering: The current state of the art (such as it is)
Authors: Varney Nils R. , Ju Daushen
Published: July 2002

While the fact of litigation in neuropsychological
assessment is about as subtle as a horse in a bedroom,
it does not necessarily follow that the nature of malingering
behaviors is also obvious or that the logic and techniques
of malingering assessment have achieved “mature”
validity. Despite the dramatic increase in studies on malingering
in recent years, detection of malingering in head injury
litigation continues to be a challenge for neuropsychologists.
Numerous studies, most published since 1994, have attempted
to search for the best technique for identifying malingering
and/or malingerers. Unfortunately, this effort has been
hampered by the lack of clinical data regarding the complexity
and diversity of malingering behaviors themselves. In addition,
the research is being conducted by clinical neuroscientists
who, in various ways, are somewhat unsophisticated in their
views of malingering detection statistics, paradigms and
proofs (vs. forensic psychologists, maybe?).
Evaluation of reading comprehension with neuropsychological
and event-related brain potential (ERP) methods
Authors: D'ARCY RYAN C.N. , CONNOLLY JOHN F. , ESKES GAIL A.
Published: July 2002

Evidence is presented for the efficacy of a new method
of assessing reading comprehension using a standardized
reading test that was formatted for computer presentation
with simultaneous event-related brain potential (ERP) recordings.
Reading comprehension abilities of 23 healthy undergraduate
students were evaluated using ERPs. The results revealed
a differential ERP response pattern for correct and incorrect
test items. These response patterns were observed at individual
participant levels. The findings provided further support
for the use of ERPs in the neuropsychological assessment
of patients who are difficult or impossible to assess using
behavioral responses because of concomitant motoric and/or
communicative limitations. (JINS, 2000, 6,
556–567.)
Longitudinal evaluation of cognitive disorder in Huntington's
disease
Authors: SNOWDEN JULIE , CRAUFURD DAVID , GRIFFITHS HELEN , THOMPSON JENNIFER , NEARY DAVID
Published: July 2002

The study investigated longitudinal change in cognitive
function in 87 patients with Huntington's disease
(HD), using a range of neuropsychological tests, which
tap mental manipulative abilities, memory, and frontal
executive skills. Over a 1-year period the largest changes
were noted in letter fluency, object recall, and Stroop
Test performance, whereas no changes were noted over more
than 3 years on the modified Wisconsin Card Sorting Test.
Contrary to expectation, greater change was evident over
1 year for tasks with low compared to high cognitive demands.
The differential sensitivity of tasks was attributed in
part to inherent characteristics of the tests themselves:
their capacity to detect minor gradations of change and
their vulnerability to practice effects. However, the greater
change for relatively automatic, speed-based tasks with
low cognitive demands was interpreted as reflecting the
evolution of HD, with a greater magnitude of change occurring
in basal ganglia than cortical function. One purpose of
the study was to identify tasks sensitive to the progression
of HD and hence most suitable for the evaluation of therapies.
Despite reaching statistical significance by virtue of
the large group size, numerical differences in test scores
over 1 year were very small, suggesting that the use of
such tests to evaluate change in individuals or small groups
of subjects would be problematic. The data highlight the
slow progression of HD, the limitations of standard cognitive
tests in detecting change over short periods, and the need
for therapeutic studies that encompass a relatively prolonged
time frame. (JINS, 2001, 7, 33–44.)
Neuropsychological functioning in cocaine abusers with and
without alcohol dependence
Authors: ROBINSON JANE E. , HEATON ROBERT K. , O'MALLEY STEPHANIE S.
Published: July 2002

Thirty codependent cocaine and alcohol users were
compared with age-, education-, race-, and sex-matched
cocaine abusers (N = 30) and normals (N
= 30) using an extended Halstead-Reitan Neuropsychological
Test Battery to determine whether cocaine abusers with
alcohol dependence were more cognitively impaired than
singly addicted cocaine abusers. Tests were grouped and
analyzed according to 8 major ability areas. Participants
who abused both cocaine and alcohol did not differ from
normals on the majority of test measures. An unexpected
but consistent finding was the poorer performance of the
cocaine sample relative to cocaine and alcohol abusers
on measures of complex psychomotor and simple motor functioning
(ps < .001). Pure cocaine abusers, but not
abusers of both cocaine and alcohol, also performed more
poorly than normals on a measure of global neuropsychological
functioning (p < .01). These results are consistent
with previous reports of generally mild cognitive dysfunction
in cocaine abusers. The findings also suggest that cocaine
and alcohol abusers of relatively young ages may be less
cognitively impaired than demographically comparable cocaine
abusers. Evidence from studies of vascular functioning
in abusers of cocaine and alcohol alone and in combination
is discussed as possible explanation for these findings.
(JINS, 1999, 5, 10–19.)
Effect of literacy on neuropsychological test performance
in nondemented, education-matched elders
Authors: MANLY JENNIFER J. , JACOBS DIANE M. , SANO MARY , BELL KAREN , MERCHANT CAROL A. , SMALL SCOTT A. , STERN YAAKOV
Published: July 2002

The current investigation compared neuropsychological
test performance among nondemented literate and illiterate
elders. The sample included participants in an epidemiological
study of normal aging and dementia in the Northern Manhattan
community. All participants were diagnosed as nondemented
by a neurologist, and did not have history of Parkinson's
disease, stroke, or head injury. Literacy level was determined
by self-report. MANOVAs revealed a significant overall
effect for literacy status (literate vs. illiterate)
on neuropsychological test performance when groups were
matched on years of education. The overall effect of literacy
status remained significant after restricting the analyses
to elders with no formal education, and after controlling
for the effects of language of test administration. Specifically,
illiterates obtained lower scores on measures of naming,
comprehension, verbal abstraction, orientation, and figure
matching and recognition. However, tests of verbal list
delayed recall, nonverbal abstraction, and category fluency
were unaffected by literacy status, suggesting that these
measures can be used to accurately detect cognitive decline
among illiterate elders in this sample. Differences in
organization of visuospatial information, lack of previous
exposure to stimuli, and difficulties with interpretation
of the logical functions of language are possible factors
that contribute to our findings. (JINS, 1999,
5, 191–202.)
Detecting significant change in neuropsychological test
performance: A comparison of four models
Authors: TEMKIN NANCY R. , HEATON ROBERT K. , GRANT IGOR , DIKMEN SUREYYA S.
Published: July 2002

A major use of neuropsychological assessment is
to measure changes in functioning over time; that is, to
determine whether a difference in test performance indicates
a real change in the individual or just chance
variation. Using 7 illustrative test measures and retest
data from 384 neurologically stable adults, this paper
compares different methods of predicting retest scores,
and of determining whether observed changes in performance
are unusual. The methods include the Reliable Change Index,
with and without correction for practice effect, and models
based upon simple and multiple regression. For all test
variables, the most powerful predictor of follow-up performance
was initial performance. Adding demographic variables and
overall neuropsychological competence at baseline significantly
but slightly improved prediction of all follow-up scores.
The simple Reliable Change Index without correction for
practice performed least well, with high error rates and
large prediction intervals (confidence intervals). Overall
prediction accuracy was similar for the other three methods;
however, different models produce large differences in
predicted scores for some individuals, especially those
with extremes of initial test performance, overall competency,
or demographics. All 5 measures from the Halstead–Reitan
Battery had residual (observed − predicted score)
variability that increased with poorer initial performance.
Two variables showed significant nonnormality in the distribution
of residuals. For accurate prediction with smallest
prediction–confidence intervals, we recommend multiple
regression models with attention to differential variability and
nonnormality of residuals. (JINS, 1999, 5,
357–369.)
Cost–benefit analysis and the environment
Authors: RAY ANANDARUP
Published: July 2002

The thrust of the principles enunciated in Arrow et al. is that economic benefits and costs can be a great help in organizing disparate concerns, in identifying issues, and in designing regulatory policies and individual projects with environmental impact. While this true, I must disagree with the authors that 'formal benefit-cost analysis should not be viewed as either necessary or sufficient for designing sensible public policy' (p. 201). At least there can be little doubt that cost-benefit analysis is necessary for sensible policy. I comment below from the perspective of devloping countries.
The role of
Polish environmental funds: Too generous or too restrictive?
Authors: ANDERSON GLEN D. , ZYLICZ TOMASZ
Published: July 2002

In many
countries, and particularly in the economies in transition in Central
and Eastern Europe, public environmental funds play an important role in
financing environmental investments. These funds provide subsidized
financing through grants and soft loans in response to market failures
that limit environmental investors' access to capital markets or poorly
account for the benefits of environmental improvements. The principal
question explored in the paper is whether environmental funds are too
generous or too selective in co-financing environmental projects. The
authors conducted a survey of applicants whose applications to Polish
environmental funds were rejected following appraisal by the funds in
1994. Applicants were contacted to determine whether they had been able
to close the financing 'gap' by the end of 1995 that had resulted from
the rejection of their application by the Fund. Survey results indicate
that a large majority of respondents have secured substitute gap
financing and proceeded with their planned investments, suggesting that
the fund's assistance was not essential for these projects to be
implemented. Generally, the financing gap had been closed by financing
from another environmental fund, from own resources, and less frequently
from the same fund (after resubmitting a modified proposal). Only in few
instances have proposed projects been abandoned.
Networked music: bridging real and virtual space
Authors: Young John P.
Published: July 2002

This paper describes an exploration of utilising the World Wide Web for interactive music. The origin of this investigation was the intermedia work Telemusic #1, by Randall Packer, which combined live performers with live public participation via the Web. During the event, visitors to the site navigated through a virtual interface, and while manipulating elements, projected their actions in the form of triggered sounds into the physical space. Simultaneously, the live audio performance was streamed back out to the Internet participants. Thus, anyone could take part in the collective realisation of the work and hear the musical results in real time. The underlying technology is, to our knowledge, the first standards-based implementation linking the Web with Cycling '74 MAX. Using only ECMAScript/JavaScript, Java, and the OTUDP external from UC Berkeley CNMAT, virtually any conceivable interaction with a Web page can send data to a MAX patch for processing. The code can also be readily adapted to work with Pd, jMAX and other network-enabled applications.
Scale invariance in biology: coincidence or footprint of a universal mechanism?
Authors: GISIGER T.
Published: July 2002

In this article, we present a self‐contained review of recent work on complex biological systems which exhibit no characteristic scale. This property can manifest itself with fractals (spatial scale invariance), flicker noise or 1/f‐noise where f denotes the frequency of a signal (temporal scale invariance) and power laws (scale invariance in the size and duration of events in the dynamics of the system). A hypothesis recently put forward to explain these scale‐free phenomomena is criticality, a notion introduced by physicists while studying phase transitions in materials, where systems spontaneously arrange themselves in an unstable manner similar, for instance, to a row of dominoes. Here, we review in a critical manner work which investigates to what extent this idea can be generalized to biology. More precisely, we start with a brief introduction to the concepts of absence of characteristic scale (power‐law distributions, fractals and 1/f‐noise) and of critical phenomena. We then review typical mathematical models exhibiting such properties: edge of chaos, cellular automata and self‐organized critical models. These notions are then brought together to see to what extent they can account for the scale invariance observed in ecology, evolution of species, type III epidemics and some aspects of the central nervous system. This article also discusses how the notion of scale invariance can give important insights into the workings of biological systems.
From Duverger to Cox, and beyond: The State-of-the-Art in Electoral Law Studies
Authors: Gaines Brian J.
Published: July 2002

Prior to its publication, Gary Cox's Making Votes Count was widely and eagerly anticipated. (Indeed, some years ago, I received a referee report dismissing my submission as unnecessary because superior analysis would eventually appear in Cox's then forthcoming manuscript.) Upon its release in 1998, the book was instantly lauded: it collected multiple awards, including the prestigious Woodrow Wilson prize for best book published on government, politics, or international affairs. This acclaim was scarcely surprising – Cox has been one of the foremost scholars of elections and legislatures for the whole of his professional career. He is responsible for an impressive body of work spanning multiple research topics, nations, and methods of analysis. This book is testimony to his breadth, as it catalogs the key electoral features of virtually the whole set of modern democracies (more than 70), and makes frequent forays into diverse nations in search of empirical support for novel theoretical findings. In brief, Cox's project is to bring together a large formal, deductive literature on voting rules and social choice with an equally voluminous empirical, inductive literature on elections and party systems in the world's democracies. The prizes it garnered are one measure of the book's success at this merger; a large boost in Cox's swelling citation count will doubtless follow, reiterating the judgement that this is the major work on electoral law and voting to date.
Insect pests of eucalypts in California: implications of managing invasive species
Authors: Paine T.D. , Millar J.G.
Published: July 2002

For the first 150 years following their introduction, eucalypts planted in the California landscape were free of both insect pests and diseases. In the last 15 years, numerous herbivorous insect species have been introduced accidentally into the State and have caused significant damage to the trees. Several of these species, e.g. Phoracantha semipunctata (Fabricius), Phoracantha recurva Newman (Coleoptera: Cerambycidae) and Gonipterus scutellatus Gyllenhal (Coleoptera: Curculionidae), have also been introduced into other parts of the world where eucalypts are grown, whereas others, e.g. Glycaspsis brimblecombei Moore (Hemiptera: Spondyliaspidae) and Eucalyptolyma maideni Froggatt (Hemiptera: Spondyliaspidae), are currently restricted to California and Australia. Research programmes have provided management solutions to individual pest problems, but as more pest species are introduced, these solutions must be integrated across broad geographic, horticultural, and economic scales, in a systems approach.
Unproductively spliced ribosomal protein mRNAs are natural targets of mRNA surveillance in C. elegans
Authors: Mitrovich Quinn M. , Anderson Philip
Published: July 2002

Messenger RNA surveillance, the selective and rapid degradation of mRNAs containing premature stop codons, occurs in all eukaryotes tested. The biological role of this decay pathway, however, is not well understood. To identify natural substrates of mRNA surveillance, we used a cDNA-based representational difference analysis to identify mRNAs whose abundance increases in Caenorhabditis elegans smg(−) mutants, which are deficient for mRNA surveillance. Alternatively spliced mRNAs of genes encoding ribosomal proteins L3, L7a, L10a, and L12 are abundant natural targets of mRNA surveillance. Each of these genes expresses two distinct mRNAs. A productively spliced mRNA, whose abundance does not change in smg(−)mutants, encodes a normal, full-length, ribosomal protein. An unproductively spliced mRNA, whose abundance increases dramatically insmg(−) mutants, contains premature stop codons because of incomplete removal of an alternatively spliced intron. In transgenic animals expressing elevated quantities of RPL-12, a greater proportion of endogenous rpl-12 transcript is spliced unproductively. Thus, RPL-12 appears to autoregulate its own splicing, with unproductively spliced mRNAs being degraded by mRNA surveillance. We demonstrate further that alternative splicing of rpl introns is conserved among widely diverged nematodes. Our results suggest that one important role of mRNA surveillance is to eliminate unproductive by-products of gene regulation.
Ku acts in a unique way at the mammalian telomere to prevent end joining
Authors: Hsu Hsin-Ling , Gilley David , Galande Sanjeev A. , Hande M. Prakash , Allen Beth , Kim Sahn-Ho , Li Gloria C. , Campisi Judith , Kohwi-Shigematsu Terumi , Chen David J.
Published: July 2002

Telomeres are specialized DNA/protein structures that act as protective caps to prevent end fusion events and to distinguish the chromosome ends from double-strand breaks. We report that TRF1 and Ku form a complex at the telomere. The Ku and TRF1 complex is a specific high-affinity interaction, as demonstrated by several in vitro methods, and exists in human cells as determined by coimmunoprecipitation experiments. Ku does not bind telomeric DNA directly but localizes to telomeric repeats via its interaction with TRF1. Primary mouse embryonic fibroblasts that are deficient for Ku80 accumulated a large percentage of telomere fusions, establishing that Ku plays a critical role in telomere capping in mammalian cells. We propose that Ku localizes to internal regions of the telomere via a high-affinity interaction with TRF1. Therefore, Ku acts in a unique way at the telomere to prevent end joining.
Coilin forms the bridge between Cajal bodies and SMN, the Spinal Muscular Atrophy protein
Authors: Hebert Michael D. , Szymczyk Piotr W. , Shpargel Karl B. , Matera A. Gregory
Published: July 2002

Spinal muscular atrophy (SMA) is a genetic disorder caused by mutations in the human survival of motor neuron 1 gene,SMN1. SMN protein is part of a large complex that is required for biogenesis of various small nuclear ribonucleoproteins (snRNPs). Here, we report that SMN interacts directly with the Cajal body signature protein, coilin, and that this interaction mediates recruitment of the SMN complex to Cajal bodies. Mutation or deletion of specific RG dipeptide residues within coilin inhibits the interaction both in vivo and in vitro. Interestingly, GST-pulldown experiments show that coilin also binds directly to SmB‘. Competition studies show that coilin competes with SmB‘ for binding sites on SMN. Ectopic expression of SMN and coilin constructs in mouse embryonic fibroblasts lacking endogenous coilin confirms that recruitment of SMN and splicing snRNPs to Cajal bodies depends on the coilin C-terminal RG motif. A cardinal feature of SMA patient cells is a defect in the targeting of SMN to nuclear foci; our results uncover a role for coilin in this process.
A sporulation membrane protein tethers the pro-ςK processing enzyme to its inhibitor and dictates its subcellular localization
Authors: Rudner David Z. , Losick Richard
Published: July 2002

The developmental transcription factor ςK is derived from the inactive precursor protein pro-ςK by regulated proteolysis during the process of sporulation in the bacteriumBacillus subtilis. The putative pro-ςK processing enzyme SpoIVFB is a member of a family of membrane-embedded metalloproteases and is held inactive by two other integral membrane proteins, SpoIVFA and BofA. Herein we show that the processing enzyme and its two regulators exist in a multimeric complex that localizes to the membrane surrounding the developing spore (the forespore). We further show that one of the regulators, SpoIVFA, plays a central role in both the formation of this complex and its subcellular localization. Evidence is presented in support of a model in which SpoIVFA acts as a platform for bringing BofA and SpoIVFB together, whereby BofA inhibits pro-ςK processing until a signal has been received from the forespore.
Genome-wide location and regulated recruitment of the RSC nucleosome-remodeling complex
Authors: Ng Huck Hui , Robert François , Young Richard A. , Struhl Kevin
Published: July 2002

Genome-wide location analysis indicates that the yeast nucleosome-remodeling complex RSC has ∼700 physiological targets and that the Rsc1 and Rsc2 isoforms of the complex behave indistinguishably. RSC is associated with numerous tRNA promoters, suggesting that the complex is recruited by the RNA polymerase III transcription machinery. At RNA polymerase II promoters, RSC specifically targets several gene classes, including histones, small nucleolar RNAs, the nitrogen discrimination pathway, nonfermentative carbohydrate metabolism, and mitochondrial function. At the histoneHTA1/HTB1 promoter, RSC recruitment requires the Hir1 and Hir2 corepressors, and it is associated with transcriptional inactivity. In contrast, RSC binds to promoters involved in carbohydrate metabolism in response to transcriptional activation, but prior to association of the Pol II machinery. Therefore, the RSC complex is generally recruited to Pol III promoters and it is specifically recruited to Pol II promoters by transcriptional activators and repressors.
The Mosaic Structure of Human Pericentromeric DNA: A Strategy for Characterizing Complex Regions of the Human Genome
Authors: Horvath Juliann E. , Schwartz Stuart , Eichler Evan E.
Published: July 2002

The pericentromeric regions of human chromosomes pose particular problems for both mapping and sequencing. These difficulties are due, in large part, to the presence of duplicated genomic segments that are distributed among multiple human chromosomes. To ensure contiguity of genomic sequence in these regions, we designed a sequence-based strategy to characterize different pericentromeric regions using a single (162 kb) 2p11 seed sequence as a point of reference. Molecular and cytogenetic techniques were first used to construct a paralogy map that delineated the interchromosomal distribution of duplicated segments throughout the human genome. Monochromosomal hybrid DNAs were PCR amplified by primer pairs designed to the 2p11 reference sequence. The PCR products were directly sequenced and used to develop a catalog of sequence tags for each duplicon for each chromosome. A total of 685 paralogous sequence variants were generated by sequencing 34.7 kb of paralogous pericentromeric sequence. Using PCR products as hybridization probes, we were able to identify 702 human BAC clones, of which a subset, 107 clones, were analyzed at the sequence level. We used diagnostic paralogous sequence variants to assign 65 of these BACs to at least 9 chromosomal pericentromeric regions: 1q12, 2p11, 9p11/q12, 10p11, 14q11, 15q11, 16p11, 17p11, and 22q11. Comparisons with existing sequence and physical maps for the human genome suggest that many of these BACs map to regions of the genome with sequence gaps. Our analysis indicates that large portions of pericentromeric DNA are virtually devoid of unique sequences. Instead, they consist of a mosaic of different genomic segments that have had different propensities for duplication. These biologic properties may be exploited for the rapid characterization of, not only pericentromeric DNA, but also other complex paralogous regions of the human genome.

[The sequence data described in this paper have been submitted to the GenBank data library under accession numbers AC002038,AC002307, AF182004-AF182009, AF183323-AF183331, AF183333-AF183337,AF183339-AF183350, AF183352-AF183356, AF183358-AF183362,AF183366-AF183369, AF183371-AF183375, and AF262624–AF262695.]
Minisatellites: Mutability and Genome Architecture
Authors: Vergnaud Gilles , Denoeud France
Published: July 2002

Minisatellites have been found in association with important features of human genome biology such as gene regulation, chromosomal fragile sites, and imprinting. Our knowledge of minisatellite biology has greatly increased in the past 10 years owing to the identification and careful analysis of human hypermutable minisatellites, experimental models in yeast, and recent in vitro studies of minisatellite recombination properties. In parallel, minisatellites have been put forward as potential biomarkers for the monitoring of genotoxic agents such as ionizing radiation. We summarize and discuss recent observations on minisatellites. In addition we take advantage of recent whole chromosome sequence data releases to provide a unifying view which may facilitate the annotation of tandem repeat sequences.
Links from Genome Proteins to Known 3-D Structures
Authors: Wang Yanli , Bryant Stephen , Tatusov Roman , Tatusova Tatiana
Published: July 2002

We describe a genome annotation service provided by the Entrez browser, http://www.ncbi.nlm.nih.gov/entrez. All protein products identified in fully sequenced microbial genomes have been compared with proteins with known 3-D structure by use of the BLAST sequence comparison algorithm. For the ∼20% of genome proteins in which unambiguous sequence similarity is detected, Entrez provides a link from the gene product to its predicted structure. The service uses the Cn3D molecular graphics viewer to present a 3-D view of the known structure, together with an alignment display mapping conserved residues from the genome protein onto the known structure. Using an example from Aeropyrum pernix, we illustrate how mapping to a 3-D structure can confirm predictions of biological function.
Analysis of the Cat Eye Syndrome Critical Region in Humans and the Region of Conserved Synteny in Mice: A Search for Candidate Genes at or near the Human Chromosome 22 Pericentromere
Authors: Footz Tim K. , Brinkman-Mills Polly , Banting Graham S. , Maier Stephanie A. , Riazi M. Ali , Bridgland Lindsay , Hu Song , Birren Bruce , Minoshima Shinsei , Shimizu Nobuyoshi , Pan HuaQin , Nguyen Thuan , Fang Fang , Fu Ying , Ray Linda , Wu Hui , Shaull Steve , Phan Stacey , Yao Ziyun , Chen Feng , Huan Axin , Hu Ping , Wang Qiaoyan , Loh Phoebe , Qi Sulan , Roe Bruce A. , McDermid Heather E.
Published: July 2002

We have sequenced a 1.1-Mb region of human chromosome 22q containing the dosage-sensitive gene(s) responsible for cat eye syndrome (CES) as well as the 450-kb homologous region on mouse chromosome 6. Fourteen putative genes were identified within or adjacent to the human CES critical region (CESCR), including three known genes (IL-17R,ATP6E, and BID) and nine novel genes, based on EST identity. Two putative genes (CECR3 and CECR9) were identified, in the absence of EST hits, by comparing segments of human and mouse genomic sequence around two solitary amplified exons, thus showing the utility of comparative genomic sequence analysis in identifying transcripts. Of the 14 genes, 10 were confirmed to be present in the mouse genomic sequence in the same order and orientation as in human. Absent from the mouse region of conserved synteny areCECR1, a promising CES candidate gene from the center of the contig, neighboring CECR4, and CECR7 andCECR8, which are located in the gene-poor proximal 400 kb of the contig. This latter proximal region, located ∼1 Mb from the centromere, shows abundant duplicated gene fragments typical of pericentromeric DNA. The margin of this region also delineates the boundary of conserved synteny between the CESCR and mouse chromosome 6. Because the proximal CESCR appears abundant in duplicated segments and, therefore, is likely to be gene poor, we consider the putative genes identified in the distal CESCR to represent the majority of candidate genes for involvement in CES.
Drosophila Euchromatic LTR Retrotransposons are Much Younger Than the Host Species in Which They Reside
Authors: Bowen Nathan J. , McDonald John F.
Published: July 2002

The recent release of the complete euchromatic genome sequence ofDrosophila melanogaster offers a unique opportunity to explore the evolutionary history of transposable elements (TEs) within the genome of a higher eukaryote. In this report, we describe the annotation and phylogenetic comparison of 178 full-length long terminal repeat (LTR) retrotransposons from the sequenced component of theD. melanogaster genome. We report the characterization of 17 LTR retrotransposon families described previously and five newly discovered element families. Phylogenetically, these families can be divided into three distinct lineages that consist of members from the canonical Copia and Gypsy groups as well as a newly discovered third group containing BEL, mazi, and rooelements. Each family consists of members with average pairwise identities ≥99% at the nucleotide level, indicating they may be the products of recent transposition events. Consistent with the recent transposition hypothesis, we found that 70% (125/178) of the elements (across all families) have identical intra-element LTRs. Using the synonymous substitution rate that has been calculated previously forDrosophila (.016 substitutions per site per million years) and the intra-element LTR divergence calculated here, the average age of the remaining 30% (53/178) of the elements was found to be 137,000 ±89,000 yr. Collectively, these results indicate that many full-length LTR retrotransposons present in the D. melanogaster genome have transposed well after this species diverged from its closest relative Drosophila simulans, 2.3 ± .3 million years ago.
Shotgun Optical Maps of the Whole Escherichia coli O157:H7 Genome
Authors: Lim Alex , Dimalanta Eileen T. , Potamousis Konstantinos D. , Yen Galex , Apodoca Jennifer , Tao Chunhong , Lin Jieyi , Qi Rong , Skiadas John , Ramanathan Arvind , Perna Nicole T. , Plunkett Guy , Burland Valerie , Mau Bob , Hackett Jeremiah , Blattner Frederick R. , Anantharaman Thomas S. , Mishra Bhubaneswar , Schwartz David C.
Published: July 2002

We have constructed NheI and XhoI optical maps ofEscherichia coli O157:H7 solely from genomic DNA molecules to provide a uniquely valuable scaffold for contig closure and sequence validation. E. coli O157:H7 is a common pathogen found in contaminated food and water. Our approach obviated the need for the analysis of clones, PCR products, and hybridizations, because maps were constructed from ensembles of single DNA molecules. Shotgun sequencing of bacterial genomes remains labor-intensive, despite advances in sequencing technology. This is partly due to manual intervention required during the last stages of finishing. The applicability of optical mapping to this problem was enhanced by advances in machine vision techniques that improved mapping throughput and created a path to full automation of mapping. Comparisons were made between maps and sequence data that characterized sequence gaps and guided nascent assemblies.
Characterization of the Genomic Xist Locus in Rodents Reveals Conservation of Overall Gene Structure and Tandem Repeats but Rapid Evolution of Unique Sequence
Authors: Nesterova Tatyana B. , Slobodyanyuk Sergey Ya. , Elisaphenko Eugene A. , Shevchenko Alexander I. , Johnston Colette , Pavlova Marina E. , Rogozin Igor B. , Kolesnikov Nikolay N. , Brockdorff Neil , Zakian Suren M.
Published: July 2002

The Xist locus plays a central role in the regulation of X chromosome inactivation in mammals, although its exact mode of action remains to be elucidated. Evolutionary studies are important in identifying conserved genomic regions and defining their possible function. Here we report cloning, sequence analysis, and detailed characterization of the Xist gene from four closely related species of common vole (field mouse), Microtus arvalis. Our analysis reveals that there is overall conservation of Xistgene structure both between different vole species and relative to mouse and human Xist/XIST. Within transcribed sequence, there is significant conservation over five short regions of unique sequence and also over Xist-specific tandem repeats. The majority of unique sequences, however, are evolving at an unexpectedly high rate. This is also evident from analysis of flanking sequences, which reveals a very high rate of rearrangement and invasion of dispersed repeats. We discuss these results in the context of Xist gene function and evolution.

[The sequence data described in this paper have been submitted to the GenBank data library under accession nos.AJ310127–AJ310130 and AJ311670.]
Genomic Evolution of the Long Terminal Repeat Retrotransposons in Hemiascomycetous Yeasts
Authors: Neuvéglise Cécile , Feldmann Horst , Bon Elisabeth , Gaillardin Claude , Casaregola and Serge
Published: July 2002

We identified putative long terminal repeat- (LTR) retrotransposon sequences among the 50,000 random sequence tags (RSTs) obtained by the Génolevures project from genomic libraries of 13 Hemiascomycetes species. In most cases additional sequencing enabled us to assemble the whole sequences of these retrotransposons. These approaches identified 17 distinct families, 10 of which are defined by full-length elements. We also identified five families of solo LTRs that were not associated with retrotransposons. Ty1-like retrotransposons were found in four of five species that are phylogenetically related to Saccharomyces cerevisiae (S. uvarum, S. exiguus, S. servazzii, and S. kluyveri but notZygosaccharomyces rouxii), and in two of threeKluyveromyces species (K. lactis and K. marxianus but not K. thermotolerans). Only multiply crippled elements could be identified in the K. lactis and S. servazziistrains analyzed, and only solo LTRs could be identified in S. uvarum. Ty4-like elements were only detected in S. uvarum,indicating that these elements appeared recently before speciation of the Saccharomyces sensu stricto species. Ty5-like elements were detected in S. exiguus, Pichia angusta, andDebaryomyces hansenii. A retrotransposon homologous with Tca2 from Candida albicans, an element absent from S. cerevisiae, was detected in the closely related species D. hansenii. A complete Ty3/gypsy element was present inS. exiguus, whereas only partial, often degenerate, sequences resembling this element were found in S. servazzii, Z. rouxii, S. kluyveri, C. tropicalis, and Yarrowica lipolytica. P. farinosa(syn. P. sorbitophila) is currently the only yeast species in which no LTR retrotransposons or remnants have been found. Thorough analysis of protein sequences, structural characteristics of the elements, and phylogenetic relationships deduced from these data allowed us to propose a classification for the Ty1/copiaelements of hemiascomycetous yeasts and a model of LTR-retrotransposon evolution in yeasts.
Biomedical Applications and Studies of Molecular Evolution: A Proposal for a Primate Genomic Library Resource: Figure 1.
Authors: Eichler Evan E. , DeJong Pieter J.
Published: July 2002

The anticipated completion of two of the most biomedically relevant genomes, mouse and human, within the next three years provides an unparalleled opportunity for the large-scale exploration of genome evolution. Targeted sequencing of genomic regions in a panel of primate species and comparison to reference genomes will provide critical insight into the nature of single-base pair variation, mechanisms of chromosomal rearrangement, patterns of selection, and species adaptation. Although not recognized as model “genetic organisms” because of their longevity and low fecundity, 30 of the ∼300 primate species are targets of biomedical research. The existence of a human reference sequence and genomic primate BAC libraries greatly facilitates the recovery of genes/genomic regions of high biological interest because of an estimated maximum neutral nucleotide sequence divergence of 25%. Primate species, therefore, may be regarded as the ideal model “genomic organisms”. Based on existing BAC library resources, we propose the construction of a panel of primate BAC libraries from phylogenetic anchor species for the purpose of comparative medicine as well as studies of genome evolution.

[The following individuals kindly provided reagents, samples, or unpublished information as indicated in the paper: J. Rogers, C. Chiu, M. Olson, L. Williams, J. Erwin, M. Rocchio, V. Casagrande, O. Ryder, J. Allman, C. Williams, and members of the La Jolla Initiative on Human Origins.]
A cGMP-Dependent Protein Kinase Gene, foraging, Modifies Habituation-Like Response Decrement of the Giant Fiber Escape Circuit in Drosophila
Authors: Engel Jeff E. , Xie Xian-Jin , Sokolowski Marla B. , Wu Chun-Fang
Published: July 2002

The Drosophila giant fiber jump-and-flight escape response is a model for genetic analysis of both the physiology and the plasticity of a sensorimotor behavioral pathway. We previously established the electrically induced giant fiber response in intact tethered flies as a model for habituation, a form of nonassociative learning. Here, we show that the rate of stimulus-dependent response decrement of this neural pathway in a habituation protocol is correlated with PKG (cGMP-Dependent Protein Kinase) activity and foraging behavior. We assayed response decrement for natural and mutant rover and sitter alleles of the foraging (for) gene that encodes a Drosophila PKG. Rover larvae and adults, which have higher PKG activities, travel significantly farther while foraging than sitters with lower PKG activities. Response decrement was most rapid in genotypes previously shown to have low PKG activities and sitter-like foraging behavior. We also found differences in spontaneous recovery (the reversal of response decrement during a rest from stimulation) and a dishabituation-like phenomenon (the reversal of response decrement evoked by a novel stimulus). This electrophysiological study in an intact animal preparation provides one of the first direct demonstrations that PKG can affect plasticity in a simple learning paradigm. It increases our understanding of the complex interplay of factors that can modulate the sensitivity of the giant fiber escape response, and it defines a new adult-stage phenotype of the foraging locus. Finally, these results show that behaviorally relevant neural plasticity in an identified circuit can be influenced by a single-locus genetic polymorphism existing in a natural population of Drosophila.
Identification, Purification, and Molecular Cloning of N-1-Naphthylphthalmic Acid-Binding Plasma Membrane-Associated Aminopeptidases from Arabidopsis
Authors: Murphy Angus S. , Hoogner Karen R. , Peer Wendy Ann , Taiz Lincoln
Published: July 2002

Polar transport of the plant hormone auxin is regulated at the cellular level by inhibition of efflux from a plasma membrane (PM) carrier. Binding of the auxin transport inhibitor N-1-naphthylphthalamic acid (NPA) to a regulatory site associated with the carrier has been characterized, but the NPA-binding protein(s) have not been identified. Experimental disparities between levels of high-affinity NPA binding and auxin transport inhibition can be explained by the presence of a low-affinity binding site and in vivo hydrolysis of NPA. In Arabidopsis, colocalization of NPA amidase and aminopeptidase (AP) activities, inhibition of auxin transport by artificial β-naphthylamide substrates, and saturable displacement of NPA by the AP inhibitor bestatin suggest that PM APs may be involved in both low-affinity NPA binding and hydrolysis. We report the purification and molecular cloning of NPA-binding PM APs and associated proteins from Arabidopsis. This is the first report of PM APs in plants. PM proteins were purified by gel permeation, anion exchange, and NPA affinity chromatography monitored for tyrosine-AP activity. Lower affinity fractions contained two orthologs of mammalian APs involved in signal transduction and cell surface-extracellular matrix interactions. AtAPM1 and ATAPP1 have substrate specificities and inhibitor sensitivities similar to their mammalian orthologs, and have temporal and spatial expression patterns consistent with previous in planta histochemical data. Copurifying proteins suggest that the APs interact with secreted cell surface and cell wall proline-rich proteins. AtAPM1 and AtAPP1 are encoded by single genes. In vitro translation products of ATAPM1 and AtAPP1 have enzymatic activities similar to those of native proteins.