bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of the effects of bupropion on the reinforcing properties of nicotine and food in rats
Authors: Bruijnzeel Adrie W. , Markou Athina 
Published: July 2003

AbstractBupropion is an atypical antidepressant drug that is the only nonnicotine‐based prescription medicine approved for smoking cessation by the Food and Drug Administration. The aim of the present experiments was to investigate the effects of bupropion (5–40 mg/kg) on the reinforcing properties of nicotine and food in rats. The effects of bupropion were studied under two schedules of reinforcement: a fixed ratio 5 time‐out 20‐sec (FR5 TO20 s) and a progressive ratio (PR). Rats were trained to respond for nicotine (0.01 or 0.03 mg/kg/infusion, free base) or food under the FR5 TO20 s schedule. Pretreatment with the highest dose of bupropion (40 mg/kg) resulted in a significant reduction (∼50%) of nicotine intake in rats self‐administering 0.03 mg/kg/infusion of nicotine. The same dose of bupropion also decreased (∼40%) the self‐administration of 0.01 mg/kg/infusion of nicotine, but this effect did not reach statistical significance. Pretreatment with bupropion slightly (∼15%) reduced responding for food under the FR5 TO20 s schedule. Finally, pretreatment with bupropion did not affect the self‐administration of nicotine (0.03 mg/kg/infusion) under a PR schedule, but dose‐dependently increased responding for food under the same PR schedule. These findings indicate that a high dose of bupropion decreases the reinforcing properties of nicotine as measured under an FR schedule, while having no apparent effects on breaking points for nicotine under a PR schedule that reflects both the reinforcing properties and the motivation to obtain nicotine. Synapse 50:20–28, 2003. © 2003 Wiley‐Liss, Inc.
Differences in multiple forms of short‐term plasticity between excitatory and inhibitory hippocampal neurons in culture
Authors: Kaplan Michael P. , Wilcox Karen S. , Dichter Marc A. 
Published: July 2003

AbstractSynaptic transmission is highly dynamic, especially during periods of repetitive activity. This short‐term synaptic plasticity, elicited by either pairs or short trains of action potentials at moderate frequencies (1–10 Hz), may give rise to either depression or facilitation of synaptic transmission. We analyzed these processes in isolated, synaptically coupled pairs of inhibitory or excitatory neurons grown in low‐density cultures of hippocampal neurons. Most inhibitory and excitatory synapses in these cultures displayed paired pulse depression, although the responses of excitatory synapses were more variable and occasionally facilitation was seen. With tetanic stimuli, inhibitory synapses showed depression, but excitatory synapses showed a much richer repertoire of behaviors, including depression and facilitation. While many inhibitory synapses showed posttetanic depression following short trains of action potentials, excitatory synapses instead showed posttetanic facilitation. This facilitation is accompanied by an increase in paired pulse ratio, suggesting that it is the result of presynaptic mechanisms. Finally, excitatory synapses often displayed paired pulse and tetanic facilitation of asynchronous release, a process not seen in inhibitory synapses in these cultures. These similarities and differences in short‐term plasticity exhibited by inhibitory and excitatory cells are likely to be critical for information processing and the control of neuronal excitability, under both normal and pathological conditions, such as epilepsy. Synapse 50:41–52, 2003. © 2003 Wiley‐Liss, Inc.
Regulation of the release of serotonin in the dorsal raphe nucleus by α1 and α2 adrenoceptors
Authors: Pudovkina Olga L. , Cremers Thomas I.F.H. , Westerink Ben H.C. 
Published: July 2003

AbstractTo investigate the modulation of serotonin release in the dorsal raphe nucleus (DRN) by α1 and α2 adrenoceptors, dual‐probe microdialysis was performed in conscious rats. The specific α1 and α2 adrenoceptor agonists and antagonists were locally infused into the DRN via retrograde microdialysis. The release of serotonin was simultaneously sampled from the DRN and prefrontal cortex (PFC). Infusion of the α1 adrenoceptor agonist cirazoline into the DRN (100 μM) produced an increase in the release of serotonin in the DRN to 200% of the basal levels, but no effect was seen in the PFC. After infusion of the α1 adrenoceptor antagonist prazosin into the DRN (100 μm) the release of serotonin decreased in the DRN and PFC to about 40% and 65% of the basal levels, respectively. Infusion of the α2 adrenoceptor agonist clonidine into the DRN (100 μm) slightly but significantly decreased the level of serotonin in the DRN as well as in the PFC to about 70% of the basal levels. Infusion of the α2A adrenoceptor antagonist BRL 44408 into the DRN (100 μm) caused an increase of serotonin release in the DRN to 270% of the basal levels, but at the same time no changes were seen in the extracellular levels of serotonin in the PFC. The present study demonstrates that α1 as well as α2 adrenoceptors in the DRN modulate the release of serotonin in the DRN, and that α1 adrenoceptors in the DRN are maximally stimulated during resting conditions. Synapse 50:77–82, 2003. © 2003 Wiley‐Liss, Inc.
Chronic opioid antagonist treatment selectively regulates trafficking and signaling proteins in mouse spinal cord
Authors: Patel Chintan N. , Rajashekara Vikram , Patel Kaushal , Purohit Vishal , Yoburn Byron C. 
Published: July 2003

AbstractChronic opioid antagonist treatment produces functional supersensitivity and μ‐opioid receptor (μOR) upregulation. Studies suggest a role for G‐protein receptor kinases (GRKs) and dynamin (DYN), but not signaling proteins (e.g., Giα2), in regulation of μOR density following opioid treatment. Therefore, this study examined μOR density, agonist potency, and the abundance and gene expression of GRK‐2, DYN‐2, and Giα2 in mouse spinal cord after opioid antagonist treatment. Mice were implanted with a 15 mg naltrexone (NTX) or placebo pellet and 8 days later pellets were removed. At 24 and 192 h following NTX treatment, mice were tested for spinal DAMGO analgesia. Other mice were sacrificed at 0 or 192 h following NTX treatment and Giα2, GRK‐2, and DYN‐2 protein and mRNA levels determined. [3H] DAMGO binding studies were also conducted. Immediately following NTX treatment (0 h), μOR density was increased (+ ≈135%), while 192 h following NTX treatment μOR density was unchanged. NTX increased DAMGO analgesic potency (3.1‐fold) 24 h following NTX treatment, while there was no effect at 192 h. NTX decreased protein and mRNA abundance of GRK‐2 (−32%; −48%) and DYN‐2 (−25%; −29%) in spinal cord at 0 h. At 192 h following 8‐day NTX treatment, GRK‐2 protein and mRNA were at control levels, while DYN‐2 protein remained decreased (–31%) even though DYN‐2 mRNA had returned to control levels. Giα2 was unaffected by NTX treatment. These data suggest that opioid antagonist‐induced μ‐receptor upregulation is mediated by changes in abundance and gene expression of proteins implicated in receptor trafficking, which may decrease constitutive receptor cycling. Synapse 50:67–76, 2003. © 2003 Wiley‐Liss, Inc.
Characterization of vps33+, a gene required for vacuolar biogenesis and protein sorting in Schizosaccharomyces pombe
Authors: Iwaki Tomoko , Osawa Fumi , Onishi Masayuki , Koga Takako , Fujita Yasuko , Hosomi Akira , Tanaka Naotaka , Fukui Yasuhisa , Takegawa Kaoru 
Published: July 2003

AbstractFrom the fission yeast Schizosaccharomyces pombe we have identified and deleted vps33, a gene encoding a homologue of VPS33, which is required for vacuolar biogenesis in S. cerevisiae cells. When the vps33+ gene is disrupted, Sz. pombe strains are temperature‐sensitive for growth and contain numerous small vesicular structures stained with FM4–64 in the cells. Deletion of the Sz. pombe vps33+ gene results in pleiotropic phenotypes consistent with the absence of normal vacuoles, including missorting of vacuolar carboxypeptidase Y, various ion‐ and drug‐sensitivities, and sporulation defects. These results are consistent with Vps33p being necessary for the morphogenesis of vacuoles and subsequent expression of vacuolar functions in Sz. pombe cells. Copyright © 2003 John Wiley & Sons, Ltd.
Investigations into the polymorphisms at the ECM38 locus of two widely used Saccharomyces cerevisiae S288C strains, YPH499 and BY4742
Authors: Kumar Chitranshu , Sharma Rakesh , Bachhawat Anand Kumar 
Published: July 2003

AbstractThe ECM38 gene encodes the γ‐glutamyl transpeptidase enzyme, an enzyme involved in glutathione turnover. The enzyme was found to be present in the S288C strain, BY4742, but absent in another widely used strain congenic to S288C, YPH499. Cloning and sequencing the genes from these yeasts indicated the presence of 11 single nucleotide polymorphisms in the coding region and eight single nucleotide polymorphisms in the promoter region of the ECM38 gene of YPH499 (but none in that of BY4742). One of the SNPs in the ECM38 ORF led to a G → D conversion in a region conserved in all γ‐GT enzymes and was found to be responsible for the loss of activity in this strain. The presence of γ‐GT activity in other YPH strains led us to trace the origins of the polymorphisms in YPH499. Our results indicated that among the progenitor strains, YPH1 and YPH2, YPH1 carried the polymorphisms seen in YPH499 and also lacked the γ‐GT activity. The implications of these results for the use of these widely used S288C strains and the origin of these single nucleotide polymorphisms are presented. Copyright © 2003 John Wiley & Sons, Ltd.
The pfr1 gene from the human pathogenic fungus Paracoccidioides brasiliensis encodes a half‐ABC transporter that is transcribed in response to treatment with fluconazole
Authors: Gray Christopher H. , Ines Borges‐Walmsley M. , Evans Gareth J. , Walmsley Adrian R. 
Published: July 2003

AbstractWe have isolated a gene that encodes a half‐ABC‐transporter, designated Pfr1, from the dimorphic human pathogenic fungus Paracoccidioides brasiliensis, which has high identity with members of the ABC‐superfamily involved in multidrug resistance. The pfr1 gene is predicted to encode a 827 amino acid protein that, in common with mammalian Mdr1, has a TM‐NBD topology. The transcription of the pfr1 gene is induced by the triazole drug fluconazole but not by amphotericin B, suggesting a role in transport‐mediated azole resistance. However, Pfr1 has greatest identity to the mitochondrial ABC transporters Mdl1 and Mdl2 from Saccharomyces cerevisiae and mammalian ABC‐me, with identities of 47.2%, 40.6% and 39.5%, respectively, over the length of these proteins. Furthermore, the N‐terminus of Pfr1 is rich in positively charged residues, a feature of mitochondrial targeting sequences. Considering these features, it seems likely that Pfr1 is a mitochondrial protein. Previous studies have revealed that the acquisition of azole resistance in S. cerevisiae is linked to mitochondrial loss and, conversely, that mitochondrial dysfunction can lead to the upregulation of PDR transporters mediated by the transcription factor Pdr3. Our studies suggest that a mitochondrial ABC transporter is induced as part of the cellular response to drug treatment. The promoter region of pfr1 contains a PDRE‐like consensus sequence to which Pdr3 binds, which may be the element responsible for the upregulation of Pfr1 in response to fluconazole. The nucleotide binding domain of Pfr1 was expressed and purified from Escherichia coli and shown to retain ATPase activity, consistent with Pfr1 functioning as a homodimeric transport ATPase. Copyright © 2003 John Wiley & Sons, Ltd.
A diverse set of nuclear RNAs transfer between nuclei of yeast heterokaryons
Authors: Olson Brian L. , Siliciano Paul G. 
Published: July 2003

AbstractSmall nuclear RNAs and small nucleolar RNAs function in the nucleus of eukaryotic cells during pre‐mRNA splicing and ribosomal RNA processing, respectively. In metazoan cells, the small nuclear RNAs shuttle between the nucleus and the cytoplasm during ribonucleoprotein particle assembly. Nuclear export of these small RNAs in yeast, however, has not been demonstrated. Therefore, we have attempted to visualize internuclear RNA movements by in situ hybridization in heterokaryon yeast cells. Using the kar1Δ15 mutation to block karyogamy, we mated two strains, each expressing a unique allele of U1 snRNA. In these heterokaryons, we observed a time‐dependent transfer of U1 snRNA from one nucleus to the other. This transfer was reduced two‐fold by the addition of the Crm1p‐inhibitor leptomycin B. Interestingly, however, we observed identical transfer of the U2 and U6 snRNAs and SNR4, SNR8, SNR9 and SNR11 snoRNAs. Remarkably, when the U2, U6 or SNR4 RNAs were observed in the same heterokaryon as the U1 snRNA, both RNAs always transferred simultaneously. These data suggest a global leaking or transport of material between nuclei of yeast heterokaryons. Our results suggest that caution must be taken when testing nuclear envelope shuttling in yeast heterokaryons. Copyright © 2003 John Wiley & Sons, Ltd.
Cloning and chromosomal mapping of URA3 genes of Pichia farinosa and P. sorbitophila encoding orotidine‐5′‐phosphate decarboxylase
Authors: Suzuki Chise , Yoshida Nao , Okano Etsuko , Kawasumi Toshiyuki , Kashiwagi Yutaka 
Published: July 2003

AbstractThe PfURA3 gene, which encodes orotidine‐5′‐phosphate decarboxylase, of osmotolerant yeast Pichia farinosa NFRI 3621, was cloned by complementation of the ura3 mutation of Saccharomyces cerevisiae. The nucleotide sequence of the PfURA3 gene and its deduced amino acid sequence indicated that the gene encodes a protein (PfUra3p) of 267 amino acids. Pulsed‐field gel electrophoresis and subsequent Southern blot analysis showed that the genome of P. farinosa NFRI 3621 consisted of seven chromosomes, each approximately 1.1–2.2 Mb in size (11.8 Mb in total) and that PfURA3 was located on chromosome V. Pichia sorbitophila is considered as a synonym of P. farinosa. The genome of P. sorbitophila IFO10021 may consist of 12 chromosomes, each approximately 1.2–2.2 Mb in size. P. sorbitophila has two copies of URA3 genes, termed PsURA3 and PsURA30, which were located on chromosome VIII and III, respectively. The difference between PfURA3 and PsURA3 was only two amino acid substitutions, whereas that between PsURA3 and PsURA30 was six amino acid substitutions and the deletion of the C‐terminal amino acid by a stop codon insertion. The sequences of PfURA3, PsURA3 and PsURA30 have been deposited in the DDBJ data library under Accession Nos AB071417, AB109042 and AB109043, respectively. Copyright © 2003 John Wiley & Sons, Ltd.
A genetic screen for yeast genes induced by sustained osmotic stress
Authors: Runner Vanessa M. , Brewster Jay L. 
Published: July 2003

AbstractThe budding yeast, Saccharomyces cerevisiae, responds to changes in external osmolarity through the activation of an osmosensing signal transduction pathway. Using lacZ–reporter gene fusions, clonal cell lines were screened for levels of β‐galactosidase activity in the presence or absence of osmotic stress. A screen of 9000 transformants displayed 663 (7%) gene fusions that were active in rich medium. Each of the transformants were also assayed for gene activity 24 h following a transfer to high osmolarity medium (0.6 M NaCl) and of the 9000 clonal cell lines, 86 (1%) displayed a decrease in expression, and seven (0.1%) displayed a reproducible increase in gene expression during primary screening. The chromosomal loci of the lacZ insertions were determined, and the gene(s) associated with that site was examined for osmotically induced expression using RNA blot analysis. Five stress‐activated genes were analysed by RNA blot: YDL222C, NMD2, PTC7, FAA4 and YRF1. The genes identified by this screen encompass cellular adaptations to stress including signal transduction, protein myristoylation and fatty acid/sphingolipid content in the cell membrane. Copyright © 2003 John Wiley & Sons, Ltd.
Parallel analysis of tagged deletion mutants efficiently identifies genes involved in endoplasmic reticulum biogenesis
Authors: Wright Robin , Parrish Mark L. , Cadera Emily , Larson Lynnelle , Matson Clinton K. , Garrett‐Engele Philip , Armour Chris , Lum Pek Yee , Shoemaker Daniel D. 
Published: July 2003

AbstractIncreased levels of HMG‐CoA reductase induce cell type‐ and isozyme‐specific proliferation of the endoplasmic reticulum. In yeast, the ER proliferations induced by Hmg1p consist of nuclear‐associated stacks of smooth ER membranes known as karmellae. To identify genes required for karmellae assembly, we compared the composition of populations of homozygous diploid S. cerevisiae deletion mutants following 20 generations of growth with and without karmellae. Using an initial population of 1557 deletion mutants, 120 potential mutants were identified as a result of three independent experiments. Each experiment produced a largely non‐overlapping set of potential mutants, suggesting that differences in specific growth conditions could be used to maximize the comprehensiveness of similar parallel analysis screens. Only two genes, UBC7 and YAL011W, were identified in all three experiments. Subsequent analysis of individual mutant strains confirmed that each experiment was identifying valid mutations, based on the mutant's sensitivity to elevated HMG‐CoA reductase and inability to assemble normal karmellae. The largest class of HMG‐CoA reductase‐sensitive mutations was a subset of genes that are involved in chromatin structure and transcriptional regulation, suggesting that karmellae assembly requires changes in transcription or that the presence of karmellae may interfere with normal transcriptional regulation. Copyright © 2003 John Wiley & Sons, Ltd.
Secular trends in acute myocardial infarction in relation to physical activity in the general Danish population
Authors: Sjøl A. , Thomsen K. K. , Schroll M. , Andersen L. B. 
Published: July 2003

Secular trends in AMI rates were analyzed in relation to physical activity levels. The population attributable risk of physical inactivity was calculated. Participants were randomly selected subjects from a suburb of Copenhagen, Denmark, screened during the years 1964–1991. Occupational physical activity and in leisure time were assessed 1964, 1974, 1976, 1982, 1987 and 1991 by self‐administered questionnaire along with smoking habits and alcohol consumption. Blood pressure, weight, height and serum lipids were measured according to WHO‐standards. Mortality data were obtained from death certificates, from hospital records or autopsies. Acute myocardial infarctions (AMI) 1964–1994 were included. 13.925 men and women aged 30, 40, 50 and 60 years, were drawn as random samples from a background population of 300.000 inhabitants. A cohort born in 1914 was examined in 1964 and 1974, a cohort born in 1936, was examined in 1976 and 1987; Monica (Monitoring trends and determinants in cardiovascular diseases) I cohort were examined in 1982 and 1987; MONICA II in 1986, and MONICA III in 1991. Mean physical activity level at leisure adjusted for age and sex increased over time (P < 0001). 25% of the men were sedentary, and more women reported a sedentary lifestyle than men. The overall trend was from 1964 to 1992 a decline in physical activity at work (P < 0001) in both gender and all age groups. The difference in AMI incidence rates between leisure time physical activity (LTPA) levels increased over time. No change was found in AMI rates comparing sedentary in different time periods. A remarkable decrease over time in the AMI incidence rate was found in physically active during leisure time. Population attributable risk (PAR) exceeded 40% in both genders in the late 1980s. In conclusion the difference in AMI rates between LTPA subgroups has increased over time. The low AMI rates observed among the most physically active reveal a substantial potential for the prevention of AMI through physical activity. A population attributable risk of more than 40% for physical inactivity suggests a potential for primary prevention through increased physical activity.
Prevention of anterior cruciate ligament injuries in female team handball players: a prospective intervention study over three seasons
Authors: Myklebust G. , Engebretsen L. , Braekken I. H. , Skjolberg A. , Olsen O. E. , Bahr R. 
Published: July 2003

Objective: To assess the effect of a neuromuscular training program on the incidence of anterior cruciate ligament injuries in female team handball players. DESIGN: Prospective intervention study.Setting: Female team handball: Division I–III in Norway.Participants: Players from the top three divisions: control season (1998–1999), 60 teams (942 players); first intervention season (1999–2000), 58 teams (855 players); second intervention season (2000–2001), 52 teams (850 players).Intervention: A five‐phase program (duration, 15 min) with three different balance exercises focusing on neuromuscular control and planting/landing skills was developed and introduced to the players in the autumn of 1999 and revised before the start of the season in 2000. The teams were instructed in the program and supplied with an instructional video, poster, six balance mats, and six wobble boards. Additionally, a physical therapist was attached to each team to follow up with the intervention program during the second intervention period.Main Outcome Measures: The number of anterior cruciate ligament injuries during the three seasons and compliance with the program.Results: There were 29 anterior cruciate ligament injuries during the control season, 23 injuries during the first intervention season (OR, 0.87; CI, 0.50–1.52; P=0.62), and 17 injuries during the second intervention season (OR, 0.64; CI, 0.35–1.18; P=0.15). In the elite division, there were 13 injuries during the control season, six injuries during the first intervention season (OR, 0.51; CI, 0.19–1.35; P=0.17), and five injuries in the second intervention season (OR, 0.37; CI, 0.13–1.05; P=0.06). For the entire cohort, there was no difference in injury rates during the second intervention season between those who complied and those who did not comply (OR, 0.52; CI, 0.15–1.82; P=0.31). In the elite division, the risk of injury was reduced among those who completed the anterior cruciate ligament injury prevention program (OR, 0.06; CI, 0.01–0.54; P=0.01) compared with those who did not.Conclusions: This study shows that it is possible to prevent anterior cruciate ligament injuries with specific neuromuscular training.
High‐intensity training with a bi‐directional bicycle pedal improves performance in mechanically unstable ankles – a prospective randomized study of 19 subjects
Authors: Høiness Per , Glott Thomas , Ingjer Frank 
Published: July 2003

A bi‐directional bicycle pedal that combines proprioceptive training and evertor strengthening has been developed for the treatment of residual instability after ankle sprains. A prospective randomized study was carried out on 19 subjects with recurrent ankle sprains and positive stress X‐ray films. The subjects were randomized to use either a bi‐directional test pedal or a traditional uni‐directional bicycle pedal and then completed a 6‐week high‐intensity training program on a cycle ergometer. Assessment of training intensity level was based on maximum oxygen uptake values, heart rate and lactate concentration in blood at various submaximal workloads. After completion of the training program, the subjects who had used the test pedal increased peak eversion torque at 180°°s−1 by 14.2% (P = 0.020), reduced figure‐of‐eight running time by 0.24 s (P = 0.003), improved single leg stance speed from 72.5% to the maximum speed of 80% (P = 0.005), and improved Karlsson functional score by 5.1 points (P = 0.005). In the control group, single leg stance improved from 56.1 to 67.8% (P = 0.018), but otherwise no significant effects were found. This study indicates that short‐term high‐intensity training with a bi‐directional pedal improves ankle performance and may be an option in the treatment of recurrent ankle sprains.