bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biological markers of cocaine addiction: implications for medications development
Authors: ELKASHEF AHMED , VOCCI FRANK 
Published: November 2003

AbstractThe search for effective medications for cocaine addiction has been elusive. The failure to find such medications so far could be due to poor understanding of the underlying biology both in the premorbid condition and following the disease state of chronic cocaine use. Population heterogeneity could be a major factor in response to medications. In an attempt to highlight the issue of biomarkers we reviewed physiological, neuroendocrine and neuroimaging studies to identify specific biological changes/markers that could be used to characterize subgroups among chronic cocaine users. Merging the biology within medications studies of cocaine abusers could prove useful for targeting specific pharmacological agents to subgroups of patients, prediction of response to medication and relapse to use.
Ultra‐rapid opiate detoxification: from clinical applications to basic science
Authors: STREEL EMMANUEL , VERBANCK PAUL 
Published: November 2003

AbstractRapid or ultra‐rapid opiate detoxification has become increasingly popular in both private and public addiction centres. These techniques seem to facilitate the transfer of opiate‐dependent patients from opiate agonist to opiate antagonist. Despite the probable complex neuropharmacological aspects involved in these procedures, their development over nearly three decades is notable for the almost complete absence of clinically relevant animal studies. This paper discusses the historical background of this occurrence, and reviews the small number of animal studies that have been conducted. Many discussions and arguments about the techniques seem to underscore their true purpose, which is not “simply to detoxify” opiate‐addicted patients but to initiate long‐term management with naltrexone. For this reason, it may be better to conceptualize these techniques not as “rapid detoxification” but as “rapid antagonist induction”.
Attitudes of speech and language therapists towards stammering: 1985 and 2000
Authors: Crichton‐Smith Isobel , Wright Jannet , Stackhouse Joy 
Published: November 2003

AbstractBackground: Past research has indicated that speech and language therapists hold some negative attitudes towards people who stammer, their parents and the treatment of stammering. However, studies on attitudes towards stammering have predominantly focussed on therapists in the USA. Recent trends towards earlier intervention suggest that more therapists in the UK will be involved in working with stammering.Aims: This study aimed to gather current attitudes of therapists in the UK and to compare them with attitudes measured 15 years previously. It also considered the impact of postgraduate training on attitudes and examined the attitudes of therapists trained in the Lidcombe Programme.Methods & Procedures: The attitudes of 261 speech and language therapists were measured in a postal survey using the Clinician Attitudes Toward Stuttering (CATS) Inventory.Outcomes & Results: The survey revealed an increase in positive attitudes towards early intervention and a reduction in negative attitudes towards people who stammer since the CATS inventory was carried out in 1985. An analysis of generalist and specialist attitudes revealed that generalists were unsure about appropriate treatments to use with people who stammer. Therapists trained in the Lidcombe Programme held some different attitudes about early intervention, people who stammer and the treatment of stammering; however, they continued to view parental counselling as a critical factor in the treatment of the preschool child.Conclusions: The survey indicated that although therapists were more positive about some aspects of stammering, the treatment of stammering remains a complex issue. All therapists working with clients who stammer would therefore benefit from undertaking ongoing professional development in this area such as additional training, liaison with colleagues and joining a special interest group.
Risk markers for SLI: a study of young language‐learning children
Authors: Conti‐Ramsden Gina , Hesketh Anne 
Published: November 2003

AbstractBackground: Adequate assessment of ‘normal variation’ versus ‘abnormal status’ is particularly difficult for clinicians working with young children who are under 5 years of age and who present with slow language development. There is therefore clinical motivation to identify possible key difficulties (or ‘risk markers’) that may distinguish children who are likely to have specific language impairment (SLI) from the variation observed in younger, normally developing children.Aims: The issue of ‘risk markers’ for SLI was explored. It is well known that the issue of markers is controversial. The view presented here is that a risk marker represents a symptom with no assumption about whether the symptom reflects a single cause or that this symptom alone identifies the disorder.Methods and Procedures: The performance of 32 children with SLI was compared with that of 32 younger normal language‐learning children on four potential risk marker tasks: non‐word repetition, digit recall, past tense provision and plural marking.Outcomes and Results: The findings suggest that processing markers, particularly non‐word repetition, have the potential for indicating SLI risk. In particular, children who fall in the bottom quarter of the normal distribution in non‐word repetition (performance below the 25th centile) appear to be at risk of SLI.Conclusions: Although these results need to be interpreted cautiously, the evidence is thought to warrant the use of non‐word repetition tasks in clinical practice.
Epigenetic Switch from Posttranscriptional to Transcriptional Silencing Is Correlated with Promoter Hypermethylation
Authors: Fojtova Miloslava , Van Houdt Helena , Depicker Anna , Kovarik Ales 
Published: November 2003

Abstract
Changes in the distribution of methylcytosine residues along a transgene locus of tobacco (Nicotiana tabacum) in relation to the type of gene silencing were studied in parental plant leaves, calli, and regenerated plants derived thereof. Parental-silenced HeLo1 (hemizygous for locus 1) plants show posttranscriptional silencing of the residing nptII (neomycin phosphotransferase II) transgene and cytosine methylation restricted to the 3′ end and center part of the transcribed region. Here, we report that with an increasing number of cell cycles, DNA methylation changes gradually, and methylation is introduced into the promoter during cell culture and more slowly in vegetatively propagated plants. After 24 months of callus in vitro cultivation, an epigenetic variant, designated locus 1E, was obtained in which cytosine methylation of symmetrical (CG and CNG) sites was almost complete within the 5′ end of the nptII-transcribed region and the 35S promoter. Further, methylation of nonsymmetrical sites appeared de novo in the promoter, whereas this type of methylation was significantly reduced in the 3′ end of the transcribed region when compared with locus 1. The newly established epigenetic patterns were stably transmitted from calli into regenerated plants and their progeny. The protein and steady-state RNA levels remained low in locus 1E, whereas with nuclear run-on assays, no detectable amounts of primary transcripts were found along the nptII gene, indicating that the methylated promoter became inactivated. The results suggest that a switch between posttranscriptional and transcriptional gene silencing could be a mechanism leading to irrevocable shut down of gene expression within a finite number of generations.
Phylogenetic Analyses and Expression Studies Reveal Two Distinct Groups of Calreticulin Isoforms in Higher Plants
Authors: Persson Staffan , Rosenquist Magnus , Svensson Karin , Galvão Rafaelo , Boss Wendy F. , Sommarin Marianne 
Published: November 2003

Abstract
Calreticulin (CRT) is a multifunctional protein mainly localized to the endoplasmic reticulum in eukaryotic cells. Here, we present the first analysis, to our knowledge, of evolutionary diversity and expression profiling among different plant CRT isoforms. Phylogenetic studies and expression analysis show that higher plants contain two distinct groups of CRTs: a CRT1/CRT2 group and a CRT3 group. To corroborate the existence of these isoform groups, we cloned a putative CRT3 ortholog from Brassica rapa. The CRT3 gene appears to be most closely related to the ancestral CRT gene in higher plants. Distinct tissue-dependent expression patterns and stress-related regulation were observed for the isoform groups. Furthermore, analysis of posttranslational modifications revealed differences in the glycosylation status among members within the CRT1/CRT2 isoform group. Based on evolutionary relationship, a new nomenclature for plant CRTs is suggested. The presence of two distinct CRT isoform groups, with distinct expression patterns and posttranslational modifications, supports functional specificity among plant CRTs and could account for the multiple functional roles assigned to CRTs.
Characterization of Leachianone G 2″ -Dimethylallyltransferase, a Novel Prenyl Side-Chain Elongation Enzyme for the Formation of the Lavandulyl Group of Sophoraflavanone G in Sophora flavescens Ait. Cell Suspension Cultures
Authors: Zhao Ping , Inoue Kenichiro , Kouno Isao , Yamamoto Hirobumi 
Published: November 2003

Abstract
Leachianone G (LG) 2′′-dimethylallyltransferase, a novel prenyl side-chain elongation enzyme, was identified in Sophora flavescens Ait. cultured cells. The enzyme transfers a dimethylallyl group to the 2′′ position of another dimethylallyl group attached at position 8 of LG to form sophoraflavanone G, a branched monoterpenoid-conjugated flavanone characteristic to this plant. This membrane-bound dimethylallyltransferase required Mg2+ (optimum concentration was 10 mm) for the reaction and had an optimum pH of 8.8. It utilized dimethylallyl diphosphate as the sole prenyl donor, and the 2′-hydroxy function in LG was indispensable to the activity. The apparent K m values for dimethylallyl diphosphate and LG were 59 and 2.3 μm, respectively. Subcellular localization of three enzymes that participated in the formation of the lavandulyl group was also investigated by sucrose density gradient centrifugation. Two prenyltransferases, naringenin 8-dimethylallyltransferase and LG 2′′-dimethylallyltransferase, were localized in the plastids, whereas 8-dimethylallylnaringenin 2′-hydroxylase, which catalyzes the crucial step in the lavandulyl-group formation, was associated with the endoplasmic reticulum. These results suggest the close cooperation between the plastids and the endoplasmic reticulum in the formation of lavandulyl groups.
Synthesis of the Arabidopsis Bifunctional Lysine-Ketoglutarate Reductase/Saccharopine Dehydrogenase Enzyme of Lysine Catabolism Is Concertedly Regulated by Metabolic and Stress-Associated Signals
Authors: Stepansky Asya , Galili Gad 
Published: November 2003

Abstract
In plants, excess cellular lysine (Lys) is catabolized into glutamic acid and acetyl-coenzyme A; yet, it is still not clear whether this pathway has other functions in addition to balancing Lys levels. To address this issue, we examined the effects of stress-related hormones, abscisic acid (ABA), and jasmonate, as well as various metabolic signals on the production of the mRNA and polypeptide of the bifunctional Lys-ketoglutarate reductase (LKR)/saccharopine dehydrogenase (SDH) enzyme, which contains the first two linked enzymes of Lys catabolism. The level of LKR/SDH was strongly enhanced by ABA, jasmonate, and sugar starvation, whereas excess sugars and nitrogen starvation reduced its level; thus this pathway appears to fulfill multiple functions in stress-related and carbon/nitrogen metabolism. Treatments with combination of hormones and/or metabolites, as well as use of ABA mutants in conjunction with the tester sugars mannose and 3-O-methyl-glucose further supported the idea that the hormonal and metabolic signals apparently operate through different signal transduction cascades. The stimulation of LKR/SDH protein expression by ABA is regulated by a signal transduction cascade that contains the ABI1-1 and ABI2-1 protein phosphatases. By contrast, the stimulation of LKR/SDH protein expression by sugar starvation is regulated by the hexokinase-signaling cascade in a similar manner to the repression of many photosynthetic genes by sugars. These findings suggest a metabolic and mechanistic link between Lys catabolism and photosynthesis-related metabolism in the regulation of carbon/nitrogen partitioning.
Translation Start Sequences Affect the Efficiency of Silencing ofAgrobacterium tumefaciensT-DNA Oncogenes
Authors: Lee Hyewon , Humann Jodi L. , Pitrak Jennifer S. , Cuperus Josh T. , Parks T. Dawn , Whistler Cheryl A. , Mok Machteld C. , Ream L. Walt 
Published: November 2003

AbstractAgrobacterium tumefaciens oncogenes cause transformed plant cells to overproduce auxin and cytokinin. Two oncogenes encode enzymes that convert tryptophan to indole-3-acetic acid (auxin): iaaM (tryptophan mono-oxygenase) and iaaH (indole-3-acetamide hydrolase). A third oncogene (ipt) encodes AMP isopentenyl transferase, which produces cytokinin (isopentenyl-AMP). Inactivation of ipt and iaaM (or iaaH) abolishes tumorigenesis. Because adequate means do not exist to control crown gall, we created resistant plants by introducing transgenes designed to elicit posttranscriptional gene silencing (PTGS) of iaaM and ipt. Transgenes that elicit silencing trigger sequence-specific destruction of the inducing RNA and messenger RNAs with related sequences. Although PTGS has proven effective against a variety of target genes, we found that a much higher percentage of transgenic lines silenced iaaM than ipt, suggesting that transgene sequences influenced the effectiveness of PTGS. Sequences required for oncogene silencing included a translation start site. A transgene encoding a translatable sense-strand RNA from the 5′ end of iaaM silenced the iaaM oncogene, but deletion of the translation start site abolished the ability of the transgene to silence iaaM. Silencing A. tumefaciens T-DNA oncogenes is a new and effective method to produce plants resistant to crown gall disease.
Ozone-Induced Cell Death in Tobacco Cultivar Bel W3 Plants. The Role of Programmed Cell Death in Lesion Formation
Authors: Pasqualini Stefania , Piccioni Claudia , Reale Lara , Ederli Luisa , Della Torre Guido , Ferranti Francesco 
Published: November 2003

Abstract
Treatment of the ozone-sensitive tobacco (Nicotiana tabacum L. cv Bel W3) with an ozone pulse (150 nL L–1 for 5 h) induced visible injury, which manifested 48 to 72 h from onset of ozone fumigation. The “classical” ozone symptoms in tobacco cv Bel W3 plants occur as sharply defined, dot-like lesions on the adaxial side of the leaf and result from the death of groups of palisade cells. We investigated whether this reaction had the features of a hypersensitive response like that which results from the incompatible plant-pathogen interaction. We detected an oxidative burst, the result of H2O2 accumulation at 12 h from the starting of fumigation. Ozone treatment induced deposition of autofluorescent compounds and callose 24 h from the start of treatment. Total phenolic content was also strongly stimulated at the 10th and 72nd h from starting fumigation, concomitant with an enhancement in phenylalanine ammonia-lyase a and phenylalanine ammonia-lyase b expression, as evaluated by reverse transcriptase-polymerase chain reaction. There was also a marked, but transient, increase in the mRNA level of pathogenesis-related-1a, a typical hypersensitive response marker. Overall, these results are evidence that ozone triggers a hypersensitive response in tobacco cv Bel W3 plants. We adopted four criteria for detecting programmed cell death in ozonated tobacco cv Bel W3 leaves: (a) early release of cytochrome c from mitochondria; (b) activation of protease; (c) DNA fragmentation by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling of DNA 3′-OH groups; and (d) ultrastructural changes characteristic of programmed cell death, including chromatin condensation and blebbing of plasma membrane. We, therefore, provide evidence that ozone-induced oxidative stress triggers a cell death program in tobacco cv Bel W3.
Interactive Effects of Jasmonic Acid, Salicylic Acid, and Gibberellin on Induction of Trichomes in Arabidopsis
Authors: Traw M. Brian , Bergelson Joy 
Published: November 2003

Abstract
Leaf trichomes protect plants from attack by insect herbivores and are often induced following damage. Hormonal regulation of this plant induction response has not been previously studied. In a series of experiments, we addressed the effects of artificial damage, jasmonic acid, salicylic acid, and gibberellin on induction of trichomes in Arabidopsis. Artificial damage and jasmonic acid caused significant increases in trichome production of leaves. The jar1-1 mutant exhibited normal trichome induction following treatment with jasmonic acid, suggesting that adenylation of jasmonic acid is not necessary. Salicylic acid had a negative effect on trichome production and consistently reduced the effect of jasmonic acid, suggesting negative cross-talk between the jasmonate and salicylate-dependent defense pathways. Interestingly, the effect of salicylic acid persisted in the nim1-1 mutant, suggesting that the Npr1/Nim1 gene is not downstream of salicylic acid in the negative regulation of trichome production. Last, we found that gibberellin and jasmonic acid had a synergistic effect on the induction of trichomes, suggesting important interactions between these two compounds.
Changes in Surface Area of Intact Guard Cells Are Correlated with Membrane Internalization
Authors: Shope Joseph C. , DeWald Daryll B. , Mott Keith A. 
Published: November 2003

Abstract
Guard cells must maintain the integrity of the plasma membrane as they undergo large, rapid changes in volume. It has been assumed that changes in volume are accompanied by changes in surface area, but mechanisms for regulating plasma membrane surface area have not been identified in intact guard cells, and the extent to which surface area of the guard cells changes with volume has never been determined. The alternative hypothesis—that surface area remains approximately constant because of changes in shape—has not been investigated. To address these questions, we determined surface area for intact guard cells of Vicia faba as they underwent changes in volume in response to changes in the external osmotic potential. We also estimated membrane internalization for these cells. Epidermal peels were subjected to external solutions of varying osmotic potential to shrink and swell the guard cells. A membrane-specific fluorescent dye was used to identify the plasma membrane, and confocal microscopy was used to acquire a series of optical paradermal sections of the guard cell pair at each osmotic potential. Solid digital objects representing the guard cells were created from the membrane outlines identified in these paradermal sections, and surface area, volume, and various linear dimensions were determined for these solid objects. Surface area decreased by as much as 40% when external osmotic potential was increased from 0 to 1.5 MPa, and surface area varied linearly with volume. Membrane internalization was approximated by determining the amount of the fluorescence in the cell's interior. This value was shown to increase approximately linearly with decreases in the cell's surface area. The changes in surface area, volume, and membrane internalization were reversible when the guard cells were returned to a buffer solution with an osmotic potential of approximately zero. The data show that intact guard cells undergo changes in surface area that are too large to be accommodated by plasma membrane stretching and shrinkage and suggest that membrane is reversibly internalized to maintain cell integrity.
Vascularization, High-Volume Solution Flow, and Localized Roles for Enzymes of Sucrose Metabolism during Tumorigenesis byAgrobacterium tumefaciens
Authors: Wächter Rebecca , Langhans Markus , Aloni Roni , Götz Simone , Weilmünster Anke , Koops Ariane , Temguia Leopoldine , Mistrik Igor , Pavlovkin Jan , Rascher Uwe , Schwalm Katja , Koch Karen E. , Ullrich Cornelia I. 
Published: November 2003

AbstractVascular differentiation and epidermal disruption are associated with establishment of tumors induced by Agrobacterium tumefaciens. Here, we address the relationship of these processes to the redirection of nutrient-bearing water flow and carbohydrate delivery for tumor growth within the castor bean (Ricinus communis) host. Treatment with aminoethoxyvinyl-glycine showed that vascular differentiation and epidermal disruption were central to ethylene-dependent tumor establishment. CO2 release paralleled tumor growth, but water flow increased dramatically during the first 3 weeks. However, tumor water loss contributed little to water flow to host shoots. Tumor water loss was followed by accumulation of the osmoprotectants, sucrose (Suc) and proline, in the tumor periphery, shifting hexose-to-Suc balance in favor of sugar signals for maturation and desiccation tolerance. Concurrent activities and sites of action for enzymes of Suc metabolism changed: Vacuolar invertase predominated during initial import of Suc into the symplastic continuum, corresponding to hexose concentrations in expanding tumors. Later, Suc synthase (SuSy) and cell wall invertase rose in the tumor periphery to modulate both Suc accumulation and descending turgor for import by metabolization. Sites of abscisic acid immunolocalization correlated with both central vacuolar invertase and peripheral cell wall invertase. Vascular roles were indicated by SuSy immunolocalization in xylem parenchyma for inorganic nutrient uptake and in phloem, where resolution allowed SuSy identification in sieve elements and companion cells, which has widespread implications for SuSy function in transport. Together, data indicate key roles for ethylene-dependent vascularization and cuticular disruption in the redirection of water flow and carbohydrate transport for successful tumor establishment.