bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of striatal dopamine neurotransmission by nitric oxide: Effector pathways and signaling mechanisms
Authors: West Anthony R. , Galloway Matthew P. , Grace Anthony A. 
Published: August 2002

AbstractAn important role for the reactive gas nitric oxide (NO) in regulating striatal dopaminergic neurotransmission was identified shortly after initial observations indicated that this unorthodox neurotransmitter mediates many of the influences of glutamatergic neurotransmission in the cerebellum, cortex, and hippocampus. While the precise actions of NO on striatal presynaptic and postsynaptic elements remain to be fully characterized, the recent application of sophisticated anatomical, neurochemical, and electrophysiological approaches to the study of nitrergic signaling has revealed that NO exerts a powerful influence both on tonic extracellular dopamine (DA) levels and phasic DA neuron spike activity via the modulation of intrinsic striatal mechanisms and striatonigral feedback loops. Although the nature of the NO‐mediated modulatory influence on DA neurotransmission was initially clouded by seemingly conflicting neurochemical observations, a growing body of literature and understanding of the diverse signaling mechanisms and effector pathways utilized by NO indicates that NO exerts a primary facilitatory influence over tonic and phasic dopaminergic neurotransmission under physiological conditions. A review of neurochemical and electrophysiological studies examining the influence of endogenous and exogenous NO on DA neurotransmission indicates that NO signaling exerts multiple effects on local striatal circuits and projection neurons involved in regulating basal ganglia output and nigrostriatal DA neuron activity. In addition to summarizing these influences, the current review focuses on the mechanisms utilized by striatal NO signaling pathways involved in modulating DA transmission at the level of the terminal and cell body and attempts to integrate these observations into a functional model of NO‐dependent regulation of basal ganglia systems. Synapse 44:227–245, 2002. © 2002 Wiley‐Liss, Inc.
Quantitative methods for tradeoff analyses
Authors: Daniels Jesse , Werner Paul W. , Bahill A. Terry 
Published: August 2002

AbstractA Corrigendum has been published for this article in Systems Engineering 4: 190–212, 2001.Practicing engineers often find the tools and techniques used for investigating alternative system designs to be cumbersome or complicated. This article will show that these systems engineering tools and techniques are in fact quite simple and can provide critical insight into how stakeholder requirements drive the engineering design process. This helps ensure that customer requirements are satisfied throughout the entire system lifecycle and aids in reducing expensive design iterations due to poorly understood or poorly documented requirements. These goals are achieved by deriving figures of merit and combining them using standard scoring functions to steer efforts towards fulfilling the customer's objectives early in the design process. Few papers in the literature capture the basic elements of tradeoff analyses in a way that entices the engineer to utilize the techniques. We have attempted to ameliorate this problem. Most of the practices presented in the literature are written from a decision analysis perspective. The success of such techniques is dependent on the expertise of the analyst in that several of the methods require considerable analyst experience for them to be employed effectively. This paper presents standardized methodologies for carrying out tradeoff analyses, which are applicable to a wide array of problems and also demonstrates that these techniques are relatively simple to use. © 2001 John Wiley & Sons, Inc. Syst Eng 4: 190–212, 2001
Genotoxicity of di‐butyl‐phthalate and di‐iso‐butyl‐phthalate in human lymphocytes and mucosal cells
Authors: Kleinsasser Norbert H. , Wallner Barbara C. , Kastenbauer Ernst R. , Weissacher Herbert , Harréus Ulrich A. 
Published: August 2002

AbstractThe genotoxicity of phthalates, widely used plasticizers, has been shown previously for di‐butyl‐phthalate (DBP) and di‐iso‐butyl‐phthalate (DiBP) in human mucosal cells of the upper aerodigestive tract in a previous study using the Comet assay. Furthermore, higher genotoxic sensitivities of patients with squamous cell carcinomas of either the larynx or the oropharynx compared to non‐tumor patients were described. Other authors have demonstrated DNA damage by a different phthalate in human lymphocytes. It was the aim of the present study to determine whether there is a correlation between the genotoxic sensitivities to DBP and its isomer DiBP in either mucosal cells or lymphocytes. The single‐cell microgel electrophoresis assay (Comet assay) was applied to detect DNA strand breaks in human epithelial cells of the upper aerodigestive tract (n=132 specimens). Human mucosa was harvested from the oropharynx in non‐tumor patients and patients with squamous cell carcinomas of the oropharynx. Laryngeal mucosa of patients with laryngeal squamous cell carcinomas was harvested as well. Peripheral lymphocytes (n=49 specimens) were separated from peripheral blood. Xenobiotics investigated were DBP, DiBP, and N′methyl‐N′‐nitro‐N‐nitrosoguanidine (MNNG) as positive control, respectively. For statistical analysis, the SPSS™ correlation analysis according to Pearson and the Wilcoxon test were performed. Genotoxicity was found for DBP and DiBP in epithelial cells and lymphocytes (P<0.001). MNNG caused severe DNA damage. In analyzing DBP and DiBP results, genotoxic impacts in mucosal cells showed an intermediate correlation (r=0.570). Correlation in lymphocytes was the same (r=0.570). Phthalates have been investigated as a potential health hazard for a variety of reasons, including possible xenoestrogenic impact, peroxisome proliferation, and membrane destabilization. The present investigation suggests a correlated DNA‐damaging impact of DBP and DiBP in human mucosal cells and in lymphocytes, respectively. Teratogenesis Carcinog. Mutagen. 21:189–196, 2001. © 2001 Wiley‐Liss, Inc.
Potential teratogenicity of di‐n‐butyltin dichloride and other dibutyltin compounds
Authors: Farr Craig H. , Reinisch Katharine , Holson Joseph F. , Neubert Diether 
Published: August 2002

AbstractThe developmental toxicity of di‐n‐butyltin dichloride (DBT‐dC) was evaluated in Wistar rats following oral administration. No maternal toxicity, embryotoxicity, or malformations were observed at 1, 2.5, or 5 mg DBT‐dC/kg body weight. Signs of maternal toxicity, including decreased food consumption, body weight gain, and thymus weight, were observed at 10 mg/kg body weight DBT‐dC. At this dose, no evidence of embryotoxicity, including such measures as total resorptions, viable fetuses, or fetal weights, was noted in any litter data. There was a slightly increased frequency of total malformations at the 10 mg/kg dose level of 4/262 treated vs. 1/269 control fetuses. All defects occurred singly with no clustering nor organ system pattern of occurrence, which would be indicative of a teratogenic effect. The no‐observed‐adverse‐effect‐level (NOAEL) for prenatal as well as maternal toxicity was considered to be 5 mg DBT‐dC/kg body weight. The interpretation and utility of previously published studies on the developmental toxicity of dibutyltin compounds are confounded by dose regimen and data reporting deficiencies. These studies suggest that, after oral administration during days 6–17 of pregnancy, the NOAEL for malformations in rats of different strains ranges from 1.7 to 5 mg/kg body weight. In these studies, the maternal LD50 was reported to be about 8 mg/kg body weight in one study but at greater than 15 mg/kg in others. Thus, the NOAEL for teratogenicity may be roughly estimated to be from one‐tenth to one‐third of the maternal LD50. When evaluated, thymus involution, a typical but reversible effect of di‐ and tri‐butyltin compounds, was also observed at 5–10 mg/kg body weight. The most susceptible time for inducing teratogenic effects is reported to be days 7–9 of pregnancy, but malformations have also been found with dosing over longer duration at lower doses. It is doubtful that the findings of malformations at highly toxic doses in animals has any health hazard significance, especially when human exposure to dibutyltins typically occurs at several orders of magnitude lower than the doses used in these studies. Further comparative pharmacokinetic studies would be necessary in order to refine the hazard characterization. Teratogenesis Carcinog. Mutagen. 21:405–415, 2001. © 2001 Wiley‐Liss, Inc.
Gender differences in science attitude‐achievement relationships over time among white middle‐school students
Authors: Mattern Nancy , Schau Candace 
Published: August 2002

AbstractFour causal models describing the longitudinal relationships between attitudes and achievement have been proposed in the literature. These models feature: (a) cross‐effects over time between attitudes and achievement, (b) influence of achievement predominant over time, (c) influence of attitudes predominant over time, or (d) no cross‐effects over time between attitudes and achievement. In an examin‐ation of the causal relationships over time between attitudes toward science and science achievement for White rural seventh‐ and eighth‐grade students, the cross‐effects model was the best fitting model form for students overall. However, when examined by gender, the no cross‐effects model exhibited the most accurate fit for White rural middle‐school girls, whereas a new model called the no attitudes‐path model exhibited the best fit for these boys. © 2002 Wiley Periodicals Inc. J Res Sci Teach 39: 324–340, 2002
Investigation of the effects of folate deficiency on embryonic development through the establishment of a folate deficient mouse model
Authors: Burgoon Jennifer M. , Selhub Jacob , Nadeau Marie , Sadler T.W. 
Published: August 2002

AbstractBackgroundFolic acid (FA) has been shown to reduce the incidence of neural tube, craniofacial, and cardiovascular defects and low birth weight. The mechanism(s) by which the vitamin is effective, however, has not been determined. Therefore, a folic acid deficient mouse model was developed.MethodsTo create a folic acid deficiency, ICR female mice were placed on a diet containing no FA and including 1% succinyl sulfathiazole (SS) for 4 weeks before mating. Control mice were fed diets with either: 1) FA and 1% SS [+SS only diet]; 2) FA [normal diet]; or 3) a breeding diet. Dams and fetuses were examined during various days of gestation.ResultsBlood analysis showed that by gestational day 18, plasma folate concentrations in the −FA+SS fed dams decreased to 1.13 ng/ml, a concentration approximately 3% of that in breeding diet fed dams (33.24 ng/ml) and 8% of that in +SS only/normal fed dams (13.59 ng/ml). RBC folate levels showed a similar decrease, whereas homocysteine concentrations increased. Reproductive outcome in the −FA+SS fed dams was poor with increased fetal deaths, decreased fetal weight, and delays in palate and heart development.ConclusionsFemale mice fed a folic acid deficient diet and 1% succinyl sulfathiazole exhibited many of the characteristics common to human folic acid deficiency, including decreased plasma and RBC folate, increased plasma homocysteine, and poor reproductive outcomes. Thus, an excellent model has been created to investigate the mechanism(s) underlying the origin of birth defects related to folic acid deficiency. Teratology 65:219–227, 2002. © 2002 Wiley‐Liss, Inc.
Atlas of rat fetal skeleton double stained for bone and cartilage
Authors: Menegola Elena , Broccia Marisa L. , Giavini Erminio 
Published: August 2002

AbstractBackgroundThe double staining of fetal skeleton for bone and cartilage is a very useful method to evidence skeletal abnormalities in laboratory animals. However, this method has been rarely used in routine developmental toxicity tests. One reason could be the difficulty of comparing the single skeletal pieces and of having reference points. In this paper the fetal rat skeleton double stained with Alizarin red S and Alcyan Blue is described in detail to produce an atlas for developmental toxicity laboratories. Teratology 64:125–133, 2001. © 2001 Wiley‐Liss, Inc.
Stage‐specific skeletal and visceral defects of the IKr‐blocker almokalant: Further evidence for teratogenicity via a hypoxia‐related mechanism
Authors: Sköld Anna‐Carin , Wellfelt Katrin , Danielsson Bengt R. 
Published: August 2002

AbstractBackgroundAs a class effect, potent IKr‐blockers have been shown to induce stage‐specific external malformations. The aim of this study was to investigate whether IKr‐blockers also induce stage‐specific visceral and skeletal defects and to further elucidate a proposed arrhythmia–hypoxia hypothesis.MethodsSingle oral doses of the selective IKr‐blocker almokalant (ALM) 25–150 μmol/kg, 7–14 dams/group, were given to Sprague‐Dawley rats on gestation days (GD) 10–14, and the fetuses were examined for malformations on GD 21. One group was pretreated with the spin‐trapping agent, α‐phenyl‐N‐t‐butylnitrone (PBN), given intraperitoneally 1 hr before ALM on GD 11.ResultsCardiac ventricular septum defects and vascular malformations were observed after dosing on GD 10–11 and, to a lesser degree, on GD 12–13. Urogenital defects, absence/malposition of the postcaval lung lobe, and attenuated diaphragm were observed mainly on GD 10–11. Skeletal examination showed a high incidence of vertebral abnormalities on thoracic level on GD 10, on lower thoracic to caudal level on GD 11, and sternebral defects were observed all days. On GD 13 brachy‐, oligo‐, and syndactyly of the forepaw were induced, and of the hindpaw on GD 14. PBN reduced the incidence of both visceral and skeletal defects.ConclusionsThe stage specificity of observed visceral and skeletal defects correlates well with what has been reported in the literature after temporary interruption of oxygen supply during the same stages of development. The protective effect by PBN present further evidence that the teratogenicity of potent IKr‐blockers is related to induction of hypoxia– reoxygenation injury due to embryonic cardiac arrhythmia. Teratology 64:292–300, 2001. © 2001 Wiley‐Liss, Inc.
Occurrence of compounds estrogenic to freshwater mussels in surface waters in an urban area
Authors: Gagné F. , Marcogliese D. J. , Blaise C. , Gendron A. D. 
Published: August 2002

AbstractEstrogens play a major role in the sexual differentiation, gonad development, and oocyte growth of most oviparous organisms. They also stimulate vitellogenesis, the formation of high‐density glycolipophosphoprotein that serves as an energy source for the developing embryo. Surface waters from the St. Lawrence River, obtained in the vicinity of an urban area (Montreal, Quebec, Canada), were studied with respect to their estrogenic potential to the freshwater mussel Elliptio complanata. Estrogenicity was measured in water extracts by means of a competitive assay of estradiol binding to cytosolic proteins and by the vitellin‐inducing ability of mussel hemolymph following direct extract injection. Surface‐water samples drawn downstream of a municipal outfall plume and in a river draining a large farming and agricultural area had high levels of total and fecal coliform bacteria. High levels of estrogen competitors were also found and were able to induce vitellins in injected mussels. Moreover, the estrogen‐competing potential of the extracts was found to be significantly correlated with total and fecal coliform bacteria (R=0.9, p<0.01) and with the levels of vitellins in the hemolymph (R=0.62, p=0.03). The results indicate that water samples drawn from within the municipal effluent plume and from a river draining an agricultural area are estrogenic to freshwater mussels. Thus, the environmental inputs of estrogens are likely to be associated with human sewage and pesticide products. © 2001 John Wiley & Sons, Inc. Environ Toxicol 16: 260–268, 2001
Detection of DNA damage in two cell lines from rainbow trout, RTG‐2 and RTL‐W1, using the comet assay
Authors: Nehls Sebastian , Segner Helmut 
Published: August 2002

AbstractScreening methods to indicate the genotoxic potential of individual chemicals or environmental mixtures rely mainly on short‐term bacterial tests. Differences in the genotoxic response of prokaryotic and eukaryotic cells necessitate the development of nonbacterial screening assays. A promising approach for this purpose could be the comet (single‐cell gel electrophoresis) assay performed with fish cells in vitro. In the present study, we evaluated the comet assay with two different fish cell lines from rainbow trout (Oncorhyhnchus mykiss), the fibroblast‐like RTG‐2 cell line established from gonad tissue, and the epitheloid RTL‐W1 cell line established from liver tissue. The cells were exposed in vitro during 2 hr to the genotoxins, 4‐nitroquinoline‐1‐oxide (NQO), and benzo(a)pyrene (BaP), as well as to environmental samples. The LOEC values for NQO were similar in both cell lines, whereas for BaP, the RTL‐W1 cells were found to be more sensitive than the RTG‐2 cells. The slopes of the concentration–response curves of the two test compounds differed between the two cell lines, with RTG‐2 cells showing a steeper slope for NQO, and RTL‐W1 cells showing a steeper slope for BaP. When exposed to environmental samples from a remediation site, the RTL‐W1 cell line, but not the RTG‐2 cell line, indicated a genotoxic potential of the samples. The differences in the genotoxic response pattern of the two cell lines could be only partly explained in relation to metabolic enzymes, cytochrome P4501A, glutathione‐S‐transferase, and xenobiotic reductase. The findings of this study demonstrate that the comet assay with fish cell lines is suitable as in vitro screening assay in environmental genotoxicity testing, but the choice of test cell line may be critical. © 2001 John Wiley & Sons, Inc. Environ Toxicol 16: 321–329, 2001
Time‐dependent accumulation of cyanobacterial hepatotoxins in flounders (Platichthys flesus) and Mussels (Mytilus edulis) from the Northern Baltic Sea
Authors: Sipiä Vesa O. , Kankaanpää Harri T. , Flinkman Juha , Lahti Kirsti , Meriluoto Jussi A. O. 
Published: August 2002

AbstractThere is only limited information about the accumulation of algal toxins in aquatic organisms in the Baltic Sea. In this study we measured total cyanobacterial hepatotoxin levels in blue mussel (Mytilus edulis) and flounderi (Platichthys flesus) tissues. Flounder were caught with gillnets from the western Gulf of Finland during July and August 1999. Blue mussels were collected from an enclosure at 3 m depth and from an artificial reef (wreck, 25–35 m depth) in the western Gulf of Finland between June and September 1999. Flounder liver and muscle samples and soft tissues of mussels were analyzed for the cyanobacterial hepatotoxins (nodularin, NODLN and/or microcystins, MCs) using an enzyme‐linked immunosorbent assay (ELISA). Results showed a time‐dependent accumulation of hepatotoxins in flounder and mussels. In flounder, the maximum concentration 399±5 (sd) ng NODLN or MC/g dry weight (dw) was found in the liver of specimens caught on 21 August 1999. No hepatotoxins were detected in muscle samples. The maximum concentration of 2150 ng±60 (sd) ng hepatotoxin/g dw was found in the mussel soft tissues collected on 20 August 1999. Temporal NODLN or MC trends indicated depuration of cyanobacterial hepatotoxin from mussels at surface level and an increase in NODLN or MC concentrations in those from the sea bed. These studies showed that despite the low cyanobacteria cell numbers the cyanobacterial hepatotoxins can accumulate in flounder and mussels. This may allow the further transfer of cyanobacterial hepatotoxins in the food web. © 2001 John Wiley & Sons, Inc. Environ Toxicol 16: 330–336, 2001
Degradation of the cyanobacterial hepatotoxin microcystin by a new bacterium isolated from a hypertrophic lake
Authors: Park Ho‐Dong , Sasaki Youhei , Maruyama Tomoko , Yanagisawa Eiji , Hiraishi Akira , Kato Kenji 
Published: August 2002

AbstractA bacterium capable of degrading microcystins‐RR, ‐YR, and ‐LR was isolated from a hypertrophic lake. The bacterium, designated Y2 and classified phenotypically as a member of the genus Sphingomonas, was shown to be distinct phylogenetically from any established species of Sphingomonas on the basis of 16S rDNA sequencing. The bacterium was tentatively identified as Sphingomonas by manual chemotaxonomy, but 16S rRNA sequencing analysis suggests that it is in fact a new species or even a new genus. When the Y2 bacterium was added to microcystins present in culture medium, the microcystins were degraded thoroughly in 4 days. The highest degradation rates of microcystins‐RR and ‐LR were 13 and 5.4 mg L−1 day−1, respectively. The degradation rates were strongly dependent on temperature and the maximum rate was at 30°C. © 2001 John Wiley & Sons, Inc. Environ Toxicol 16: 337–343, 2001
An SSB encoded by and operating on linear killer plasmids from Kluyveromyces lactis
Authors: Schaffrath Raffael , Meacock Peter A. 
Published: August 2002

AbstractThe Kluyveromyces lactis linear plasmids k1 and k2 belong to the family of protein‐primed linear DNA genomes, which includes adenoviruses. Here we identify the 18 kDa gene product of k2ORF5 as a novel putative single‐stranded DNA binding protein, SSB. As judged from Western analysis using an epitope‐tagged fusion protein and ssDNA–agarose affinity chromatography, the Orf5 protein preferentially binds to ssDNA in vitro. Consistently, electrophoretic mobility shift assays demonstrate that ssDNA plasmid probes from k1 and k2 are retarded by this Orf5‐associated SSB activity. ORF5 gene shuffle‐mediated mutagenesis in vivo results in k1/k2 plasmid instability, pointing towards a role for the Orf5 protein in plasmid replication. Consistently, the Orf5 protein protects ssDNA from exonuclease digestion and stimulates Klenow enzyme. Our findings suggest a functional role for the Orf5 protein as a putative SSB probably required during k1/k2 plasmid DNA synthesis. Copyright © 2001 John Wiley & Sons, Ltd.
Functional analysis of the hexose transporter homologue HXT5 in Saccharomyces cerevisiae
Authors: Diderich Jasper A. , Merijn Schuurmans J. , Van Gaalen Monique C. , Kruckeberg Arthur L. , Van Dam Karel 
Published: August 2002

AbstractThe HXT5 gene encodes a functional hexose transporter that has moderate affinity for glucose (Km=10 mM), moderate to low affinity for fructose (Km=40 mM) and low affinity for mannose (Km>100 mM). The sole presence of Hxt5p in an otherwise hexose transport null mutant is sufficient to sustain a flux through glycolysis from glucose to fermentative products. However, the presence of HXT5 as the sole hexose transporter gene results in extremely poor growth on glucose, which suggests the involvement of glucose repression in the transcriptional regulation of HXT5. From Northern blot analysis on the members of the HXT family and studies with HXT5 tagged with the green fluorescent protein (GFP), it is evident that HXT5 is transcribed and translated during conditions of relatively slow growth, during growth on non‐fermentable carbon sources and in particular during sporulation. In wild‐type batch cultivations on fermentable carbon sources, Hxt5p is abundant in stationary phase or after depletion of the fermentable carbon source, which seems independent of the carbon source. The deletion of HXT5 does not result in a clear phenotype. A shift of stationary phase cells to fresh glucose medium resulted in somewhat slower resumption of growth in the hxt5 deletion strain compared to the wild‐type strain. The abundance of Hxt5p during stationary phase, sporulation and low glucose conditions suggests that HXT5 is a ‘reserve’ transporter, which might be involved in the initial uptake of glucose after the appearance of glucose. Other possible functions of the protein encoded by HXT5 will be discussed in the context of the results. Copyright © 2001 John Wiley & Sons, Ltd.