bluuebunny/crossref_metadata_2025 huggingface dataset:
Wavelength tuning of InAs quantum dots grown on InP (100) by chemical-beam epitaxy
Authors: Gong Q. , Nötzel R. , van Veldhoven P. J. , Eijkemans T. J. , Wolter J. H.
Published: January 2004

We report on an effective way to continuously tune the emission wavelength of InAs quantum dots (QDs) grown on InP (100) by chemical-beam epitaxy. The InAs QD layer is embedded in a GaInAsP layer lattice matched to InP. With an ultrathin GaAs layer inserted between the InAs QD layer and the GaInAsP buffer, the peak wavelength from the InAs QDs can be continuously tuned from above 1.6 μm down to 1.5 μm at room temperature. The major role of the thin GaAs layer is to greatly suppress the As/P exchange during the deposition of InAs and subsequent growth interruption under arsenic flux, as well as to consume the segregated surface In layer floating on the GaInAsP buffer layer.
Quantitative Trait Analysis Reveals Transforming Growth Factor-β2 as a Positive Regulator of Early Hematopoietic Progenitor and Stem Cell Function
Authors: Langer Jessica C. , Henckaerts Els , Orenstein Jonathan , Snoeck Hans-Willem
Published: January 2004

Elucidation of pathways involved in mouse strain–dependent variation in the hematopoietic stem cell (HSC) compartment may reveal novel mechanisms relevant in vivo. Here, we demonstrate genetically determined variation in the proliferation of lin−Sca1++kit+ (LSK) primitive hematopoietic progenitor cells in response to transforming growth factor-β (TGF-β) 2, the dose response of which was biphasic with a stimulatory effect at low concentrations. In contrast, the dose responses of TGF-β1 or -β3 were inhibitory and did not show mouse strain–dependent variation. A quantitative trait locus (QTL) for the effect of TGF-β2 was identified on chromosome 4 overlapping with a QTL regulating the frequency of LSK cells. These overlapping QTL were corroborated by the observation that the frequency of LSK cells is lower in adult Tgfb2+/− mice than in wild-type littermates, indicating that TGF-β2 is a genetically determined positive regulator LSK number in vivo. Furthermore, adult Tgfb2+/− mice have a defect in competitive repopulation potential that becomes more pronounced upon serial transplantation. In fetal TGF-β2–deficient HSCs, a defect only appears after serial reconstitution. These data suggest that TGF-β2 can act cell autonomously and is important for HSCs that have undergone replicative stress. Thus, TGF-β2 is a novel, genetically determined positive regulator of adult HSCs.
Gene Expression Profiling of Hairy Cell Leukemia Reveals a Phenotype Related to Memory B Cells with Altered Expression of Chemokine and Adhesion Receptors
Authors: Basso Katia , Liso Arcangelo , Tiacci Enrico , Benedetti Roberta , Pulsoni Alessandro , Foa Robin , Di Raimondo Francesco , Ambrosetti Achille , Califano Andrea , Klein Ulf , Favera Riccardo Dalla , Falini Brunangelo
Published: January 2004

Hairy cell leukemia (HCL) is a chronic B cell malignancy characterized by the diffuse infiltration of bone marrow and spleen by cells displaying a typical “hairy” morphology. However, the nature of the HCL phenotype and its relationship to normal B cells and to other lymphoma subtypes remains unclear. Using gene expression profiling, we show here that HCL displays a homogeneous pattern of gene expression, which is clearly distinct from that of other B cell non-Hodgkin lymphomas. Comparison with the gene expression profiles of purified normal B cell subpopulations, including germinal center (GC), pre-GC (naive), and post-GC (memory) B cells, shows that HCL cells are more related to memory cells, suggesting a derivation from this B cell population. Notably, when compared with memory cells, HCL cells displayed a remarkable conservation in proliferation, apoptosis, and DNA metabolism programs, whereas they appeared significantly altered in the expression of genes controlling cell adhesion and response to chemokines. Finally, these analyses have identified several genes that are specifically expressed in HCL and whose expression was confirmed at the protein level by immunocytochemical analysis of primary HCL cases. These results have biological implications relevant to the pathogenesis of this malignancy as well as clinical implications for its diagnosis and therapy.
Identification of Antibiotic Stress-Inducible Promoters: A Systematic Approach to Novel Pathway-Specific Reporter Assays for Antibacterial Drug Discovery
Authors: Fischer Hans Peter , Brunner Nina A. , Wieland Bernd , Paquette Jesse , Macko Ludwig , Ziegelbauer Karl , Freiberg Christoph
Published: January 2004

As present antibiotics therapy becomes increasingly ineffectual, new technologies are required to identify and develop novel classes of antibacterial agents. An attractive alternative to the classical target-based approach is the use of promoter-inducible reporter assays for high-throughput screening. The wide usage of these assays is, however, limited by the small number of specifically responding promoters that are known at present. This work describes a novel approach for identifying genetic regulators that are suitable for the design of pathway-specific assays. The basis for the proposed strategy is a large set of antibiotics-triggered expression profiles (“Reference Compendium”). Pattern recognition algorithms applied to the expression data pinpoint the relevant transcription-factor-binding sites in whole-genome sequences. Using this technique, we constructed a fatty-acid-pathway-specific reporter assay that is based on a novel stress-inducible promoter. In a proof-of-principle experiment, this assay was shown to enable screening for new small-molecule inhibitors of bacterial growth.
Coelomata and Not Ecdysozoa: Evidence From Genome-Wide Phylogenetic Analysis
Authors: Wolf Yuri I. , Rogozin Igor B. , Koonin Eugene V.
Published: January 2004

Relative positions of nematodes, arthropods, and chordates in animal phylogeny remain uncertain. The traditional tree topology joins arthropods with chordates in a coelomate clade, whereas nematodes, which lack a coelome, occupy a basal position. However, the current leading hypothesis, based on phylogenetic trees for 18S ribosomal RNA and several proteins, joins nematodes with arthropods in a clade of molting animals, Ecdysozoa. We performed a phylogenetic analysis of over 500 sets of orthologous proteins, which are represented in plants, animals, and fungi, using maximum likelihood, maximum parsimony, and distance methods. Additionally, to increase the statistical power of topology tests, the same methods were applied to concatenated alignments of subunits of eight conserved macromolecular complexes. The majority of the methods, when applied to most of the orthologous clusters, both concatenated and individual, grouped the fly with humans to the exclusion of the nematode, in support of the coelomate phylogeny. Trees were also constructed using information on insertions and deletions in orthologous proteins, combinations of domains in multidomain proteins, and presence-absence of species in clusters of orthologs. All of these approaches supported the coelomate clade and showed concordance between evolution of protein sequences and higher-level evolutionary events, such as domain fusion or gene loss.
Computational Gene Prediction Using Multiple Sources of Evidence
Authors: Allen Jonathan E. , Pertea Mihaela , Salzberg Steven L.
Published: January 2004

This article describes a computational method to construct gene models by using evidence generated from a diverse set of sources, including those typical of a genome annotation pipeline. The program, called Combiner, takes as input a genomic sequence and the locations of gene predictions from ab initio gene finders, protein sequence alignments, expressed sequence tag and cDNA alignments, splice site predictions, and other evidence. Three different algorithms for combining evidence in the Combiner were implemented and tested on 1783 confirmed genes in Arabidopsis thaliana. Our results show that combining gene prediction evidence consistently outperforms even the best individual gene finder and, in some cases, can produce dramatic improvements in sensitivity and specificity.
EnsMart: A Generic System for Fast and Flexible Access to Biological Data
Authors: Kasprzyk Arek , Keefe Damian , Smedley Damian , London Darin , Spooner William , Melsopp Craig , Hammond Martin , Rocca-Serra Philippe , Cox Tony , Birney Ewan
Published: January 2004

The EnsMart system (www.ensembl.org/EnsMart) provides a generic data warehousing solution for fast and flexible querying of large biological data sets and integration with third-party data and tools. The system consists of a query-optimized database and interactive, user-friendly interfaces. EnsMart has been applied to Ensembl, where it extends its genomic browser capabilities, facilitating rapid retrieval of customized data sets. A wide variety of complex queries, on various types of annotations, for numerous species are supported. These can be applied to many research problems, ranging from SNP selection for candidate gene screening, through cross-species evolutionary comparisons, to microarray annotation. Users can group and refine biological data according to many criteria, including cross-species analyses, disease links, sequence variations, and expression patterns. Both tabulated list data and biological sequence output can be generated dynamically, in HTML, text, Microsoft Excel, and compressed formats. A wide range of sequence types, such as cDNA, peptides, coding regions, UTRs, and exons, with additional upstream and downstream regions, can be retrieved. The EnsMart database can be accessed via a public Web site, or through a Java application suite. Both implementations and the database are freely available for local installation, and can be extended or adapted to `non-Ensembl' data sets.
High-Throughput MALDI-TOF Discovery of Genomic Sequence Polymorphisms
Authors: Stanssens Patrick , Zabeau Marc , Meersseman Geert , Remes Gwen , Gansemans Yannick , Storm Niels , Hartmer Ralf , Honisch Christiane , Rodi Charles P. , Böcker Sebastian , van den Boom Dirk
Published: January 2004

We describe a comparative sequencing strategy that is based on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analyses of complete base-specific cleavage reactions of a target sequence. The target is converted to a DNA/RNA mosaic structure after PCR amplification using in vitro transcription. Cleavage with defined specificity is achieved by ribonucleases. The set of cleavage products is subjected to mass spectrometry without prior fractionation. The presented resequencing assay is particularly useful for single-nucleotide polymorphism (SNP) discovery. The combination of mass spectra from four complementary cleavage reactions detects approximately 98% of all possible homozygous and heterozygous SNPs in target sequences with a length of up to 500 bases. In general, both the identity and location of the sequence variation are determined. This was exemplified by the discovery of SNPs in the human gene coding for the cholesteryl ester transfer protein using a panel of 96 genomic DNAs.
Bichir HoxA Cluster Sequence Reveals Surprising Trends in Ray-Finned Fish Genomic Evolution
Authors: Chiu Chi-hua , Dewar Ken , Wagner Günter P. , Takahashi Kazuhiko , Ruddle Frank , Ledje Christina , Bartsch Peter , Scemama Jean-Luc , Stellwag Edmund , Fried Claudia , Prohaska Sonja J. , Stadler Peter F. , Amemiya Chris T.
Published: January 2004

The study of Hox clusters and genes provides insights into the evolution of genomic regulation of development. Derived ray-finned fishes (Actinopterygii, Teleostei) such as zebrafish and pufferfish possess duplicated Hox clusters that have undergone considerable sequence evolution. Whether these changes are associated with the duplication(s) that produced extra Hox clusters is unresolved because comparison with basal lineages is unavailable. We sequenced and analyzed the HoxA cluster of the bichir (Polypterus senegalus), a phylogenetically basal actinopterygian. Independent lines of evidence indicate that bichir has one HoxA cluster that is mosaic in its patterns of noncoding sequence conservation and gene retention relative to the HoxA clusters of human and shark, and the HoxAα and HoxAβ clusters of zebrafish, pufferfish, and striped bass. HoxA cluster noncoding sequences conserved between bichir and euteleosts indicate that novel cis-sequences were acquired in the stem actinopterygians and maintained after cluster duplication. Hence, in the earliest actinopterygians, evolution of the single HoxA cluster was already more dynamic than in human and shark. This tendency peaked among teleosts after HoxA cluster duplication.
Developmental Roles of Pufferfish Hox Clusters and Genome Evolution in Ray-Fin Fish
Authors: Amores Angel , Suzuki Tohru , Yan Yi-Lin , Pomeroy Jordan , Singer Amy , Amemiya Chris , Postlethwait John H.
Published: January 2004

The pufferfish skeleton lacks ribs and pelvic fins, and has fused bones in the cranium and jaw. It has been hypothesized that this secondarily simplified pufferfish morphology is due to reduced complexity of the pufferfish Hox complexes. To test this hypothesis, we determined the genomic structure of Hox clusters in the Southern pufferfish Spheroides nephelus and interrogated genomic databases for the Japanese pufferfish Takifugu rubripes (fugu). Both species have at least seven Hox clusters, including two copies of Hoxb and Hoxd clusters, a single Hoxc cluster, and at least two Hoxa clusters, with a portion of a third Hoxa cluster in fugu. Results support genome duplication before divergence of zebrafish and pufferfish lineages, followed by loss of a Hoxc cluster in the pufferfish lineage and loss of a Hoxd cluster in the zebrafish lineage. Comparative analysis shows that duplicate genes continued to be lost for hundreds of millions of years, contrary to predictions for the permanent preservation of gene duplicates. Gene expression analysis in fugu embryos by in situ hybridization revealed evolutionary change in gene expression as predicted by the duplication-degeneration-complementation model. These experiments rule out the hypothesis that the simplified pufferfish body plan is due to reduction in Hox cluster complexity, and support the notion that genome duplication contributed to the radiation of teleosts into half of all vertebrate species by increasing developmental diversification of duplicate genes in daughter lineages.
Elevated Rates of Protein Secretion, Evolution, and Disease Among Tissue-Specific Genes
Authors: Winter Eitan E. , Goodstadt Leo , Ponting Chris P.
Published: January 2004

Variation in gene expression has been held responsible for the functional and morphological specialization of tissues. The tissue specificity of genes is known to correlate positively with gene evolution rates. We show here, using large data sets, that when a gene is expressed highly in a small number of tissues, its protein is more likely to be secreted and more likely to be mutated in genetic diseases with Mendelian inheritance. We find that secreted proteins are evolving at faster rates than nonsecreted proteins, and that their evolutionary rates are highly correlated with tissue specificity. However, the impact of secretion on evolutionary rates is countered by tissue-specific constraints that have been held constant over the past 75 million years. We find that disease genes are underrepresented among intracellular and slowly evolving housekeeping genes. These findings illuminate major selective pressures that have shaped the gene repertoires expressed in different mammalian tissues.
Crystal structure of human dipeptidyl peptidase IV in complex with a decapeptide reveals details on substrate specificity and tetrahedral intermediate formation
Authors: Aertgeerts Kathleen , Ye Sheng , Tennant Mike G. , Kraus Michelle L. , Rogers Joe , Sang Bi‐Ching , Skene Robert J. , Webb David R. , Prasad G. Sridhar
Published: January 2004

Dipeptidyl peptidase IV (DPPIV) is a member of the prolyl oligopeptidase family of serine proteases. DPPIV removes dipeptides from the N terminus of substrates, including many chemokines, neuropeptides, and peptide hormones. Specific inhibition of DPPIV is being investigated in human trials for the treatment of type II diabetes. To understand better the molecular determinants that underlie enzyme catalysis and substrate specificity, we report the crystal structures of DPPIV in the free form and in complex with the first 10 residues of the physiological substrate, Neuropeptide Y (residues 1–10; tNPY). The crystal structure of the free form of the enzyme reveals two potential channels through which substrates could access the active site—a so‐called propeller opening, and side opening. The crystal structure of the DPPIV/tNPY complex suggests that bioactive peptides utilize the side opening unique to DPPIV to access the active site. Other structural features in the active site such as the presence of a Glu motif, a well‐defined hydrophobic S1 subsite, and minimal long‐range interactions explain the substrate recognition and binding properties of DPPIV. Moreover, in the DPPIV/tNPY complex structure, the peptide is not cleaved but trapped in a tetrahedral intermediate that occurs during catalysis. Conformational changes of S630 and H740 between DPPIV in its free form and in complex with tNPY were observed and contribute to the stabilization of the tetrahedral intermediate. Our results facilitate the design of potent, selective small molecule inhibitors of DPPIV that may yield compounds for the development of novel drugs to treat type II diabetes.
Plate 307. Roscoea praecox
Authors: Cowley Jill
Published: January 2004

The taxonomy, distribution, ecology and cultivation requirements of Roscoea praecox(Zingiberaceae), a native of Yunnan Province, China, are discussed and a full description of the species is provided.
Plate 331. Huernia macrocarpa and Huernia kennedyana
Authors: Brodie Sue
Published: January 2004

The history, taxonomy, distribution, habitat and cultivation requirements of Huernia macrocarpa ssp. macrocarpa (A. Rich) Sprenger from Ethiopa and Huernia kennedyana Lavranos, a South African endemic, are discussed; the two species are fully described and colour illustrations are provided.
Plate 335. Impatiens columbaria
Authors: Grimshaw John M.
Published: January 2004

The taxonomy, distribution, ecology and cultivation requirements of Impatiens columbaria (Balsaminaceae), a native of Gabon, are discussed; there is a full description of the species, accompanied by a colour plate and floral dissection drawings.
Plants in Peril, 24: Notes on lowland African violets (Saintpaulia) in the wild
Authors: Clarke G. P.
Published: January 2004

Saintpaulia (Gesneriaceae) is confined in the wild to small patches of forest in East Africa (Tanzania and Kenya), with most of the species occurring in submontane or montane forest. However, a few species are known from lowland forests and this paper outlines the distribution and ecology of some of the species recorded from lowland sites. Additional sites for S. confusa B.L. Burtt, S. diplotricha B.L. Burtt, S. grotei Engl., S. ionantha H. Wendl, S. tongwensis B.L. Burtt and two, possibly new, species, have been located during recent field studies. One of the critically endangered species, S. tongwensis has featured previously in Curtis's Botanical Magazine (N.S. t. 11) and its illustration and description are repeated here.
Plate 345. Vanilla polylepis
Authors: La Croix Isobyl , Bell Sandra
Published: January 2004

The history, taxonomy, distribution, habitat and cultivation of the tropical African Vanilla polylepis (Orchidaceae) are discussed; a full botanical description and illustrations are also provided.
Plate 346. Choisya dumosa var. arizonica
Authors: Matthews Victoria
Published: January 2004

The history, taxonomy, distribution, habitat and cultivation of Choisya dumosa (Torr.) A. Gray var. arizonica (Standley) L. Benson (Rutaceae), a shrub native to the south‐western United States, are discussed; a botanical description and illustrations are also provided. Choisya ternata Kunth and its cultivar Sundance® are also considered, as is ‘Aztec Pearl’, a hybrid between C. ternata and C. dumosa var. arizonica.
Plate 370. Falcatifolium taxoides
Authors: Mill Robert R. , Thomas Philip
Published: January 2004

Falcatifolium taxoides (Brongn. & Gris) de Laub. (Podocarpaceae), an endemic of New Caledonia, is illustrated and its history, taxonomy, distribution, ecology and cultivation requirements are discussed; a full description is given. Brief notes on the other species of the genus and the allied genus Dacrydium are provided.
Plate 374. Cephalipterum drummondii
Authors: Smith Sarah , Staniforth Martin
Published: January 2004

The taxonomic history, distribution, habitat and cultivation requirements of Cephalipterum drummondii A. Gray (Compositae), an Australian endemic, are discussed; a full description and illustrations of the species are provided and achene characters are shown by means of Scanning Electron Micrographs.
Plate 390. Paeonia turcica
Authors: Özhatay Neriman , Page Martin , Sinnott Mike
Published: January 2004

The Turkish peony, Paeonia turcica Davis & Cullen (Paeoniaceae) is illustrated; its botanical history, medicinal and ethnobotanical uses, relationships, distribution and cultural requirements are discussed and a full description of the species is provided.
Plate 392. Fritillaria uva‐vulpis
Authors: Rix Martyn
Published: January 2004

The taxonomy, relationships, distribution and cultural requirements of Fritillaria uva‐vulpis Rix (Liliaceae), a native of south‐eastern Turkey, northern Iraq and western Iran, are discussed. An illustration is provided and a full description is given.
Plate 394. Fritillaria stenanthera
Authors: Rix Martyn
Published: January 2004

The taxonomy, relationships, distribution and cultural requirements of the central Asiatic Fritillaria stenanthera (Regel) Regel (Liliaceae) are discussed, an illustration is provided and a full description is given.
Plate 418. Calanthe striata
Authors: Cribb Phillip , Bailes Christopher
Published: January 2004

The taxonomy, relationships, distribution and cultural requirements of the Japanese Calanthe striata R.Br. (Orchidaceae) are discussed; a colour illustration and dissection drawings are provided, together with a full description.
Plate 455. Meconopsis Henrici Papaveraceae
Authors: Grey‐Wilson Christopher , Hall Tony
Published: January 2004

The Chinese Meconopsis henrici Bureau & Franch. (Papaveraceae) is illustrated. Its taxonomy and natural distribution are discussed, a full description is provided and recommendations are given for its cultivation.
EEG Diagnostic Procedures and Special Investigations in the Assessment of Photosensitivity
Authors: Rubboli Guido , Parra Jaime , Seri Stefano , Takahashi Takeo , Thomas Pierre
Published: January 2004

Summary:  Photosensitivity can be assessed in laboratory conditions with different methods. The most common procedure is intermittent photic stimulation (IPS), whose effectiveness in detecting photosensitivity depends largely on methodologic aspects. Although IPS is a widespread and routinely used procedure in EEG laboratories, only recently has a standardization of the IPS method been proposed. Furthermore, other modalities of visual stimulation, including pattern stimulation and low‐luminance visual stimulation (LLVS), have proven their usefulness in detecting photosensitivity. We provide an overview of the methodologic aspects and clinical implications of these procedures, resulting from recent consensus meetings, and the diagnostic usefulness of the LLVS technique in photosensitive individuals whose seizures are triggered particularly by television images. Finally, we briefly illustrate the potential of advanced neurophysiological (magnetoencephalography and high‐density EEG) and functional imaging techniques in the investigation of the pathophysiologic mechanisms underlying photosensitivity.
Epilepsy and Videogames
Authors: Bureau Michelle , Hirsch Edouard , Vigevano Federico
Published: January 2004

Summary: Since the first case of videogame (VG) epilepsy was reported in 1981, many cases of seizures triggered by VGs were reported, not only in photosensitive, but also in non–photosensitive children and adolescents with epilepsy. We provide an overview of the literature with overall conclusions and recommendations regarding VG playing. Specific preventive measures concerning the physical characteristics of images included in commercially available VGs (flash rate, choice of colors, patterns, and contrast) can lead in the future to a clear decrease of this problem. In addition to the positive effect of such measures, the collaborative studies performed in France and in the rest of Europe have stressed the importance of a safe distance to the screen of ≥2 m, and the less provocative role of 100‐Hz screens.
Visual Stimuli in Daily Life
Authors: Kasteleijn‐Nolst Trenité Dorothée G. A. , Van Der Beld Gerrit , Heynderickx Ingrid , Groen Paul
Published: January 2004

Summary:  People of all ages, but especially children and adolescents, are increasingly exposed to visual stimuli. Typical environmental stimuli that can trigger epileptic seizures in susceptible persons are televisions (TVs), computers, videogames (VGs), discothèque lights, venetian blinds, striped walls, rolling stairs (escalators), striped clothing, and sunlight reflected from snow or the sea or interrupted by trees during a ride in a car or train. Less common stimuli are rotating helicopter blades, disfunctioning fluorescent lighting, welding lights, etc. New potentially provocative devices turn up now and then unexpectedly. During the last decades especially, displays have become increasingly dominant in many of our daily‐life activities. We therefore focus mainly on the characteristics of artificial light and on current and future developments in video displays and videogames. Because VG playing has been shown also to have positive effects, a rating system might be developed for provocativeness to inform consumers about the content. It is important that patients with epilepsy be informed adequately about their possible visual sensitivity.
Visual Reflex Seizures Induced by Complex Stimuli
Authors: Zifkin Benjamin G. , Inoue Yushi
Published: January 2004

Summary:  Visual reflex seizures induced by complex stimuli may be triggered by patterned and flashing displays that are now ubiquitous. The seizures may be clinically generalized, but unilateral and bilateral myoclonic attacks also may be triggered, especially in patients with juvenile myoclonic epilepsy, and recently, clearly focal reflex occipital lobe seizures have been described. Some seizure‐triggering properties of video displays can be identified, such as perceived brightness, pattern, flicker frequency, and color. Knowledge of these is useful in planning individual treatment and in designing regulations for screen content of television broadcasts or for other video displays. Some subjects will also be sensitive to cognitive or action‐programming activation, especially when playing video games, and this can increase the chance of seizure triggering. Nonspecific factors such as sleep deprivation, prolonged exposure, and drug or alcohol use also may play a role in reflex seizure occurrence.
Treatment of Photosensitivity
Authors: Covanis Athanasios , Stodieck Stefan R. G. , Wilkins Arnold J.
Published: January 2004

Summary:  Not all visually sensitive patients need antiepileptic drug treatment, and even those who do can benefit from additional preventive measures. Visually provoked seizures, in particular, can be prevented or treated by avoiding or altering the triggering stimulus. Apart from individual preventive measures (use of specific television or video screens, colored glasses, etc.), prevention and warning on a larger scale are helpful. The choice for drug treatment will depend on the type of stimulus, the environment in which the person has to live and work, the frequency and severity of seizures, and the type of epileptic syndrome. A review is given of all treatment options with focus on the specific nonpharmacologic and pharmacologic tools used in clinical practice.
Regulations: What Next?
Authors: Harding Graham F. A. , Takahashi Takeo
Published: January 2004

Summary:  Television (TV) is the most provocative visual stimulus and evokes (first) seizures in susceptible children and adolescents, especially when flickering and patterned images are shown. This has led to the initiative to develop guidelines for broadcasters. The development of new types of TV screens will not remove the need for control of broadcast material. It could be argued that rather than protect the whole viewing audience by application of broadcasting guidelines, only those who are photosensitive should be protected. But maybe we should do both, because most known sensitive patients will benefit from greater safety and will not be dependent on fashionable ideas by commercial broadcasters that are not (yet) familiar with the guidelines. No such guidelines exist for video material, electronic screen games, and the Internet. It would be wise to adopt the guidelines for video material and electronic screen games.
Genetics of Photosensitivity (Photoparoxysmal Response): A Review
Authors: Stephani Ulrich , Tauer Ulrike , Koeleman Bobby , Pinto Dalila , Neubauer Bernd A. , Lindhout Dick
Published: January 2004

Summary: We present a review of phenotype–genotype correlation and the genetics of photosensitivity. The photoparoxysmal response in EEG (PPR) is still one of the best paradigms for exogenously triggered brain responses based on a genetic predisposition. The definition of the PPR phenotype requires multiple, precise methodologic guidelines. Individual factors such as age and gender but also other, unknown factors influence the expression of the PPR. For example, PPRs occur during adolescence and can disappear at a later age. As a consequence, it is difficult to assign nonaffected disease status correctly. Autosomal dominant inheritance has been found in clinical studies of relatives of PPR‐positive epilepsy and nonepilepsy subjects. Genetic heterogeneity of the PPR is obvious because the PPR also can be evoked in a number of autosomal recessive diseases. PPR is most commonly associated with idiopathic generalized epilepsies (IGEs) such as juvenile myoclonic epilepsy (JME). This comorbidity suggests that a genetic factor involved in photosensitivity also may influence the susceptibility for JME. Finding the gene for PPR also might represent a step forward in unraveling the genetic background of JME. The search for the genetic factors causing PPRs should focus on the genes affected in such epilepsies, such as genes (coding) for ion channels and neurotransmitters and their receptors. The expression of defined proteins with as‐yet‐undetermined functions, is changed in a few types of epilepsies with a mendelian mode of inheritance. These additional genes and the human equivalents of the genes found to be mutated in animal models also are candidates for molecular genetic studies of the PPR.
Physiology of Human Photosensitivity
Authors: Wilkins Arnold J. , Bonanni Paolo , Porciatti Vittorio , Guerrini Renzo
Published: January 2004

Summary:  Human epileptic photosensitivity has been studied in several ways. (a) Visual stimulation that resembles the stimulation normally responsible for seizures, such as that from televisions or videogames, both of which typically use cathode ray tubes in which the display is created in a flickering pattern. Such stimulation is often rendered yet more epileptogenic by programmes with content that also involves flashing or patterned material. (b) Elementary visual stimuli that enable inferences to be drawn concerning the physiological trigger mechanisms. The topographic distribution of epileptiform EEG activity in response to such stimuli has complemented this approach, leading to the inference that the trigger is cortical and requires sychronised mass action of neurons. (c) Stimuli that avoid paroxysmal EEG activity and permit an investigation of the subepileptic response to visual stimuli, using the evoked potential. This has revealed abnormalities in the cortical mechanisms that control the response to strong visual stimulation.
Photosensitivity: The Magnitude of the Problem
Authors: De Bittencourt Paulo R. M.
Published: January 2004

Summary:  Very few studies of photosensitivity or visual sensitive epilepsy could be called epidemiologic in the strict sense, that is, giving well‐based incidence and prevalence rates of a well‐defined clinical and electroencephalographic syndrome or group of syndromes. The available data suggest that photosensitivity is rare in the population as a whole, with an annual incidence rate around one case per 100,000 population. The incidence goes up to almost six per 100,000 in the late adolescent period, the age group at the highest risk. Well‐established concepts, such as statements that one in 4,000 of the general population or that 10% of all epilepsy patients would be photosensitive, should be reevaluated. The more likely figures are a lifetime prevalence of one in 10,000 in the general population, perhaps as low as 2%, of the epilepsy population. Further epidemiologic studies, sensu strictu, are warranted to settle the basic question of the real incidence and prevalence of photoparoxysmal responses (PPRs) and epilepsy with seizures provoked by visual stimuli in the community.
Epileptic Syndromes and Visually Induced Seizures
Authors: Guerrini Renzo , Genton Pierre
Published: January 2004

Summary:  Seizures induced by photic (or visual) stimuli or photosensitive seizures can be observed in generalized or focal, idiopathic, or symptomatic epilepsies, in progressive neurodegenerative disorders, and even in the context of situation‐related (acute symptomatic) seizures. In addition to this “transversal” presence of the photosensitive trait across various epilepsy types and diseases, some syndromes in which all, or almost all, seizures are induced by photic stimuli seem to have sufficient specificity and may be considered as syndromes of pure reflex photosensitive epilepsy. Here we review the clinical characteristic of the different types of photic‐induced seizures and the main epileptic syndromes that are characterized by visual sensitivity either as the sole manifestation or as an accessory feature.
Restoration of hair growth in mice with an alopecia areata‐like disease using topical anthralin
Authors: Tang L. , Cao L. , Sundberg J. P. , Lui H. , Shapiro J.
Published: January 2004

Abstract:  Anthralin is a widely used topical anti‐psoriatic drug that may have an immunomodulating effect on alopecia areata (AA) as it does in psoriasis. The aims of the present study were to investigate the effects of anthralin on hair growth in balding C3H/HeJ mice affected by an AA‐like disease and to study the underlying mechanisms. Affected C3H/HeJ mice were treated daily for 10 weeks on half of the dorsal skin with 0.2% anthralin and the contra‐lateral side was treated with the vehicle ointment. The percentage of surface hair coverage and hair density was graded weekly for both sides and hair growth indices were calculated using these two variables. Hair regrowth was observed in 9/14 mice on the treated sides. Four mice displayed near complete replacement of normal density and length hairs. All the vehicle‐treated sides showed either no change or continued hair loss. An RNase protection assay (RPA) showed that expression of tumor necrosis factor‐α (TNF‐α) and ‐β were inhibited by anthralin upon successful treatment. It appears that anthralin may be an effective therapy for C3H/HeJ mice with AA and certain cytokines may be involved in the therapeutic effects of anthralin on restoring hair regrowth in AA‐affected C3H/HeJ mice.
Solar‐simulated irradiation evokes a persistent and biphasic IL‐1α response
Authors: Luo Dan , Yaar Mina , Tsai Angel , Gilchrest Barbara A.
Published: January 2004

Abstract:  Exposure of skin to solar‐simulated irradiation generates a multitude of adaptive responses including cytokine transcription, synthesis and secretion. Interleukin‐1 (IL‐1) is one of the cytokines induced in epidermal cells in response to UV irradiation. It displays a broad range of mitogenic and inflammatory activities including fibroblast proliferation and T‐cell activation. There are two forms, IL‐1α and IL‐1β; and IL‐1α is the predominant form secreted by epidermal keratinocytes. UV‐induced modulations of IL‐1α message levels have been extensively studied within the first 48 h after irradiation, but longer term changes and impact on IL‐1α cellular protein levels are virtually unexplored. We now report that cells of keratinocyte origin (SCC 12F) respond to a single physiologic dose of solar‐simulated irradiation with both early (8 h) and late (72 h) peaks of IL‐1α mRNA induction. UV‐stimulated IL‐1α secretion is increased above sham‐irradiated control secretion for at least 96 h after irradiation. Our study provides evidence that UV‐induced adaptive cutaneous responses persist for at least several days, and suggests that different mechanisms may mediate the early vs. late inductions.
Pyloric atresia‐junctional epidermolysis bullosa syndrome showing novel 594insC/Q425P mutations in integrin β4 gene (ITGB4)
Authors: Masunaga Takuji , Ishiko Akira , Takizawa Yasuko , Kim Soo‐Chan , Lee Jin‐Sung , Nishikawa Takeji , Shimizu Hiroshi
Published: January 2004

Abstract:  Pyloric atresia‐junctional epidermolysis bullosa syndrome (PA‐JEB) is an autosomal recessive inherited rare blistering disorder caused by mutations in ITGA6 or ITGB4, genes encoding integrin α6 or β4, respectively. In this study, we have disclosed the mutations in ITGB4 in a Korean patient with PA‐JEB. The proband, who showed skin blisters, was diagnosed as having pyloric atresia and died 2 years after birth. Mutational analysis showed a novel 594insC maternal mutation in exon 7, which led to premature termination codon (PTC), and a novel Q425P paternal mutation in exon 11. Q425P mutation was not detected in 200 alleles obtained from a normal healthy Korean control, and was shown to reduce α‐helix forming ability in integrin β4 a by Garnier α‐helicity plot of the protein, indicating that this mutation is pathogenic but not polymorphism. The phenotype in the present case can be explained by (1) the combination of PTC and missense mutation, and (2) amino‐acid substitution occurring for the amino acid not preserved in the integrin β family. Our results contribute to further the accumulation of mutation data for better understanding of the genotype/phenotype correlation in PA‐JEB, and may give profound insight into the role of integrins α6 and β4.
Retinol, at concentrations greater than the physiological limit, induces oxidative stress and apoptosis in human dermal fibroblasts
Authors: Gimeno Amparo , Zaragozá Rosa , Vivó‐Sesé Inma , Viña Juan R. , Miralles Vicente J.
Published: January 2004

Abstract:  We have investigated the dose (in the range of μM) and time‐dependent effects of four different retinoids (retinol, retinal, retinoic acid and retinol palmitate) on human dermal fibroblasts cultivated in vitro. Retinol and retinal, at a concentration of 20 µM, caused cell damage as evaluated by lactate dehydrogenase activity released into the culture medium. The oxidised glutathione (GSSG)/reduced glutathione (GSH) ratio and malondialdehyde production indicated that 20 µM of retinol provoked oxidative stress in the cultivated human fibroblasts. In the first 8 h after retinol treatment the levels of p53 and Bax proteins as well as caspase 3 activity increased, suggesting apoptotic cell death during the first hours of treatment. If the retinol treatment exceeded 18–24 h we observed necrotic cell death. Vitamin E and coenzyme Q10 had a protective effect against oxidative stress generated by retinol. Both antioxidant molecules reduced retinol uptake, and in the case of vitamin E the expression of CRABP‐II mRNA was induced, providing a plausible explanation for its protective effect.
Presence of bactericidal/permeability‐increasing protein in human and rat skin
Authors: Takahashi Masae , Horiuchi Yoshitaka , Tezuka Tadashi
Published: January 2004

Abstract:  To examine the presence of bactericidal/permeability‐increasing protein (BPI) in skin, which is an antibacterial protein, has cytotoxicity toward Gram‐negative bacteria, and may have an important role against bacterial infection in the skin, immunohistochemical and biochemical analyses were performed. Anti‐BPI/KLH Ab reacted with the cytoplasm of the inner root sheath cells of both human and rat hair follicles by immunohistochemical examination. A protein band in 10‐M alkaline urea extracts of human scalp skin or 7‐day‐old rat skin reacted with an antibody against BPI conjugated with KLH (anti‐BPI/KLH Ab). Purified skin BPI (sBPI) from rat was a single protein spot and reacted with both anti‐BPI/KLH Ab and a commercially available monoclonal antibody against BPI (anti‐BPI MoAb). Moreover, sBPI possessed inhibitory activity against LPS. Bactericidal/permeability‐increasing protein mRNA was expressed not only in leukocytes but also in human scalp skin and cultured keratinocytes. These findings suggest that sBPI could exist in the inner root sheath cells of human and rat hair follicles, and might play a role as a barrier against anaerobic bacteria in the isthmus of hair follicles.
Killing efficacy of a new silicon phthalocyanine in human melanoma cells treated with photodynamic therapy by early activation of mitochondrion‐mediated apoptosis
Authors: Barge Jérôme , Decréau Richard , Julliard Michel , Hubaud Jean‐Claude , Sabatier Anne‐Sophie , Grob Jean‐Jacques , Verrando Patrick
Published: January 2004

Abstract:  Photodynamic therapy (PDT) is a promising therapeutic modality that utilizes a combination of a photosensitizer and visible light for the destruction of diseased tissues. Using human‐pigmented melanoma cells, we examined the photokilling efficacy of new silicon‐phthalocyanines (SiPc) that bore bulky axial substituents. The bis(cholesteryloxy) derivate (Chol‐O‐SiPc) displayed the best in vitro photokilling efficacy (LD50 = 6–8 × 10−9 M) and was seven to nine times more potent than chloro‐aluminium Pc (ClAlPc), a known photosensitizer used as a reference. Although Chol‐O‐SiPc was half as potent as ClAlPc for promoting photo‐oxidative membrane damage in a cell‐free assay, early events of mitochondrion‐mediated apoptosis upon PDT were triggered much faster, as demonstrated by kinetics studies examining cells with permeabilized mitochondrial membranes, cytochrome c release and caspase‐9 activation. Inhibition of caspase‐9 activity by a substrate analogue argued for its central role in the proapoptotic events leading to cell death by Chol‐O‐SiPc PDT. In addition, immunoblots showed that Bcl‐2 antiapoptotic oncoprotein was not a primary target of Chol‐O‐SiPc in M3Dau cells treated with PDT. Conclusively, Chol‐O‐SiPc is a useful new photosensitizer with the property of triggering cell apoptosis mediated by mitochondria.
Connections between nerve endings and epidermal cells: are they synapses?
Authors: Chateau Yannick , Misery Laurent
Published: January 2004

Abstract: Based on electron microscopy and confocal scanning microscopy, contacts between sensory axons and the cells of the epidermis have been described: with keratinocytes, Langerhans cells, melanocytes and Merkel cells. We would like to initiate a debate on this question: “Are neuro‐epidermal connections synapses?”. Anatomically, neuro‐epidermal junctions can be considered as synapses in our opinion. If neuro‐epidermal junctions are synapses, they probably belong to the family of en passant synapses, with nerve endings passing along epidermal cells and occasionally connecting to them. In conclusion, we suggest that neuro‐epidermal junctions could be considered as true synapses, but this does not exclude non synaptic interactions.
How the Brain Processes Causal Inferences in Text
Authors: Mason Robert A. , Just Marcel Adam
Published: January 2004

Theoretical models of text processing, such as the construction-integration framework, pose fundamental questions about causal inference making that are not easily addressed by behavioral studies. In particular, a common result is that causal relatedness has a different effect on text reading times than on memory for the text: Whereas reading times increase linearly as causal relatedness decreases, memory for the text is best for events that are related by a moderate degree of causal relatedness and is poorer for events with low and high relatedness. Our functional magnetic resonance imaging study of the processing of two-sentence passages that varied in their degree of causal relatedness suggests that the inference process can be analyzed into two components, generation and integration, that are subserved by two large-scale cortical networks (a reasoning system in dorsolateral prefrontal cortex and the right-hemisphere language areas). These two cortical networks, which are distinguishable from the classical left-hemisphere language areas, approximately correspond to the two functional relations observed in the behavioral results.
Unemployment Alters the Set Point for Life Satisfaction
Authors: Lucas Richard E. , Clark Andrew E. , Georgellis Yannis , Diener Ed
Published: January 2004

According to set-point theories of subjective well-being, people react to events but then return to baseline levels of happiness and satisfaction over time. We tested this idea by examining reaction and adaptation to unemployment in a 15-year longitudinal study of more than 24,000 individuals living in Germany. In accordance with set-point theories, individuals reacted strongly to unemployment and then shifted back toward their baseline levels of life satisfaction. However, on average, individuals did not completely return to their former levels of satisfaction, even after they became reemployed. Furthermore, contrary to expectations from adaptation theories, people who had experienced unemployment in the past did not react any less negatively to a new bout of unemployment than did people who had not been previously unemployed. These results suggest that although life satisfaction is moderately stable over time, life events can have a strong influence on long-term levels of subjective well-being.
The Peculiar Longevity of Things Not So Bad
Authors: Gilbert Daniel T. , Lieberman Matthew D. , Morewedge Carey K. , Wilson Timothy D.
Published: January 2004

Intense hedonic states trigger psychological processes that are designed to attenuate them, and thus intense states may abate more quickly than mild states. Because people are unaware of these psychological processes, they may mistakenly expect intense states to last longer than mild ones. In Study 1, participants predicted that the more they initially disliked a transgressor, the longer their dislike would last. In Study 2, participants predicted that their dislike for a transgressor who hurt them a lot would last longer than their dislike for a transgressor who hurt them a little, but precisely the opposite was the case. In Study 3, participants predicted that their dislike for a transgressor who hurt them a lot would last longer than their dislike for a transgressor who hurt someone else a lot, but precisely the opposite was the case. These errors of prediction are discussed as instances of a more general phenomenon known as the region-β paradox.