bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterizing the role of enterohepatic recycling in the interactions between mycophenolate mofetil and calcineurin inhibitors in renal transplant patients by pharmacokinetic modelling
Authors: Cremers Serge , Schoemaker Rik , Scholten Eduard , Den Hartigh Jan , König‐Quartel Jacqueline , Van Kan Eric , Paul Leendert , De Fijter Johan 
Published: August 2005

BackgroundControversy remains about the interaction between mycophenolate mofetil (MMF) and the calcineurin inhibitors cyclosporin (CsA) and tacrolimus (TACR). The need to double the dose of MMF in case of CsA co‐administration to achieve the same mycophenolic acid (MPA) levels as in TACR co‐administration, has been attributed to either inhibition by CsA of the enterohepatic cycle, or an inhibition of glucuronidation to mycophenolate glucuronide (MPAG) by TACR. We explored these interactions clinically in 64 kidney transplant patients.MethodsPlasma MPA/MPAG curves were determined during the first year post transplantation. Using nonlinear mixed effect modelling, MPA/MPAG data were fitted to a four‐compartment  model,  in  which  a  rate  constant  describing  transfer  from  the  fourth  to the first compartment (k41), and therefore enterohepatic recycling, could be introduced.ResultsMPA and MPAG plasma concentrations were adequately described by a four‐compartment model, which was significantly improved by introduction of k41 in case of TACR co‐administration (minimum value of the objective function decreased by 181 points, P < 0.0001). Using this model, no statistically significant difference was observed in clearance of MPA between TACR and CsA co‐administration (11.9 and 14.1 l h−1, respectively). Total clearance of MPAG was lower in case of CsA co‐administration (1.45 and 0.92 l h−1, respectively), while there was no difference in renal clearance of MPAG (1.09 and 0.92 l h−1, respectively).ConclusionsOur study supplies supportive clinical evidence that inhibition of the enterohepatic cycle in case of CsA co‐administration explains some of the differences observed in PK of MMF when co‐administered with either TACR or CsA. This finding may have clinical consequences for the immunosuppressive management of kidney transplant patients.
Pharmocokinetics and pharmacodynamics of single‐dose triazolam: electroencephalography compared with the Digit‐Symbol Substitution Test
Authors: Greenblatt David J. , Gan Lu , Harmatz Jerold S. , Shader Richard I. 
Published: August 2005

AimsTo investigate whether the electroencephalogram (EEG) directly reflects the CNS effects of benzodiazepines by evaluating the relation of the EEG to plasma drug concentrations and to Digit‐Symbol Substitution Test (DSST) scores after a single dose of triazolam, a representative benzodiazepine agonist.MethodsThirteen healthy male subjects were given 0.375 mg triazolam or placebo in a double‐blind crossover study. Plasma samples were collected during 8 h after dosage. Pharmacodynamic effects were measured by DSST and EEG at corresponding times.ResultsPharmacokinetic parameters for triazolam were consistent with established values. Compared with placebo, triazolam significantly impaired psychomotor performance on the DSST (P < 0.001) and increased beta amplitude on the EEG (P < 0.002). DSST and EEG changes both closely tracked changes in plasma concentrations over time. The changes for the two measures were highly correlated with each other (r =–0.94, P < 0.001) based on aggregate values at individual time points. However, the variations in area under the curve of pharmacodynamic effect vs. time (AUCeffect) measured by either method did not reflect the variations in plasma AUC across individuals. The individual variability in AUCeffect from the EEG was similar to that measured by the DSST.ConclusionsBoth the EEG and the DSST reflect the central benzodiazepine agonist effects of triazolam. Intrinsic variability in both measures is similar.
Nutrient limitation and enzyme activities during litter decomposition of nine wetland species in relation to litter N : P ratios
Authors: GÜSEWELL S. , FREEMAN C. 
Published: August 2005

Summary

Litter decomposition can be limited by nitrogen or phosphorus, but conditions under which either nutrient is limiting remain uncertain. We investigated whether this depends on nutrient limitation during plant growth, on N : P ratios of the litter, or on activities of C‐, N‐ and P‐mineralizing enzymes.
Nine herbaceous species were grown at N : P supply ratios (N : Ps) of 5–160 (mass‐based). Fresh leaf litter was incubated in the laboratory for 5–10 weeks, partly with N or P fertilization, to determine mass loss and activities of extracellular enzymes.
Both plant growth and litter decomposition were N‐limited for plants grown at N : Ps < 20, and P‐limited for those grown at N : Ps ≥ 40. Litter N : P ratios varied widely among species and did not predict which nutrient limited decomposition, except that litter with N : P > 22 always had P‐limited decomposition.
The activities of β‐glucosidase, chitobiase and phosphatase differed widely among species but were poorly related to litter nutrient concentrations and mass loss. Within some species, phosphatase activity increased towards high litter N : P ratios, suggesting P limitation of decomposers.
We conclude that there is no unique critical N : P ratio discriminating between N‐ and P‐limited decomposition because this critical N : P ratio is species‐dependent and may also depend on the physical conditions under which plants were grown.
Responses to stress of Caenorhabditis elegans populations with different reproductive strategies
Authors: ÁLVAREZ O. ALDA , JAGER T. , KOOIJMAN S. A. L. M. , KAMMENGA J. E. 
Published: August 2005

Summary

Hermaphroditic and gonochoric reproduction are essentially different reproductive strategies that may lead to diverging population responses to adverse environmental conditions. Each strategy implies different physiological mechanisms, which affect life‐history traits and represent different ways of dealing with stress.
We studied the performance of hermaphroditic vs gonochoric strains in the nematode Caenorhabditis elegans exposed to cadmium stress at the individual and population level.
Under control conditions, the gonochoric strain started reproduction earlier than the hermaphroditic strain at a smaller size. This was due to an earlier switch from sperm to oocyte production triggered by male sperm availability. Under cadmium stress hermaphrodites showed a decrease in the size at onset of reproduction, presumably as a strategy to maintain a high population growth rate. In contrast the body size of gonochoric nematodes was not affected.
A process‐based model (DEBtox) was used as a tool for analysing life‐history data and calculating population growth rates. The model fitted the data well using physiologically relevant parameters such as ageing, survival or reproduction related parameters. The simultaneous fit of all life‐history traits was used to obtain populations growth rate estimates.
The differences between the two C. elegans strains were reflected at the population level. Lower population growth rates, as calculated by DEBtox, were found in the gonochoric strain, largely determined by the proportion of males in the offspring.
From the overall results we suggest that the differences found between both populations are due to the reproductive strategy. Under control conditions, CB strain (with gonochoric reproduction) does not favour population growth rates in the short term due to faster ageing and copulation costs on survival. Furthermore, in response to stress this strain also showed lower performance than the N2 hermaphroditic strain, mainly due to a higher sensitivity of survival to the stressor.
Does water transport scale universally with tree size?
Authors: MEINZER F. C. , BOND B. J. , WARREN J. M. , WOODRUFF D. R. 
Published: August 2005

SummaryWe employed standardized measurement techniques and protocols to describe the size dependence of whole‐tree water use and cross‐sectional area of conducting xylem (sapwood) among several species of angiosperms and conifers.The results were not inconsistent with previously proposed 3/4‐power scaling of water transport with estimated above‐ground biomass. However, for a given size, angiosperms transported considerably greater quantities of water than conifers.In the angiosperms studied, the scaling of water transport with sapwood area, stem diameter and above‐ground biomass was best described by sigmoid functions rather than a power function, consistent with the previously reported size dependence of other processes such as growth.At least three distinct species groupings for relationships between sapwood area and stem basal area were observed. Scaling of sapwood area with stem radius was well described by a power function of the formY = Y0Xb. However, exponents obtained for two of the three species groups differed significantly from a recently proposed theoretical value of 2·33.
Soil organic matter and litter chemistry response to experimental N deposition in northern temperate deciduous forest ecosystems
Authors: Gallo M. E. , Lauber C. L. , Cabaniss S. E. , Waldrop M. P. , Sinsabaugh R. L. , Zak D. R. 
Published: August 2005

AbstractThe effects of atmospheric nitrogen (N) deposition on organic matter decomposition vary with the biochemical characteristics of plant litter. At the ecosystem‐scale, net effects are difficult to predict because various soil organic matter (SOM) fractions may respond differentially. We investigated the relationship between SOM chemistry and microbial activity in three northern deciduous forest ecosystems that have been subjected to experimental N addition for 2 years. Extractable dissolved organic carbon (DOC), DOC aromaticity, C : N ratio, and functional group distribution, measured by Fourier transform infrared spectra (FTIR), were analyzed for litter and SOM. The largest biochemical changes were found in the sugar maple–basswood (SMBW) and black oak–white oak (BOWO) ecosystems. SMBW litter from the N addition treatment had less aromaticity, higher C : N ratios, and lower saturated carbon, lower carbonyl carbon, and higher carboxylates than controls; BOWO litter showed opposite trends, except for carbonyl and carboxylate contents. Litter from the sugar maple–red oak (SMRO) ecosystem had a lower C : N ratio, but no change in DOC aromaticity. For SOM, the C : N ratio increased with N addition in SMBW and SMRO ecosystems, but decreased in BOWO; N addition did not affect the aromaticity of DOC extracted from mineral soil. All ecosystems showed increases in extractable DOC from both litter and soil in response to N treatment. The biochemical changes are consistent with the divergent microbial responses observed in these systems. Extracellular oxidative enzyme activity has declined in the BOWO and SMRO ecosystems while activity in the SMBW ecosystem, particularly in the litter horizon, has increased. In all systems, enzyme activities associated with the hydrolysis and oxidation of polysaccharides have increased. At the ecosystem scale, the biochemical characteristics of the dominant litter appear to modulate the effects of N deposition on organic matter dynamics.
Low levels of vitamin B12 and venous thromboembolic disease in elderly men
Authors: DÍAZ DE TUESTA A. M. , RIBÓ MA. D. R. , BELINCHÓN O. , MARCHENA P. J. , BRUSCAS MA. J. , VAL E. , CORTÉS A. , NIETO J. A. 
Published: August 2005

Abstract.  Díaz de Tuesta AM, Ribó MaDR, Belinchón O, Marchena PJ, Bruscas MaJ, Val E, Cortés A, Nieto JA (Virgen de la Luz Hospital, Cuenca, Spain). Low levels of vitamin B12 and venous thromboembolic disease in elderly men. J Intern Med 2005; 258: 244–249.Objectives.  Hyperhomocysteinaemia is a well‐known risk factor for venous thromboembolic disease (VTD). However, it is not clear whether homocysteine (Hc) itself or a related metabolite or a cofactor is primarily responsible for VTD. We carried out a case–control study to investigate whether vitamin concentrations that are involved in the Hc metabolism are associated or not with an elevated risk of VTD.Design.  Case–control study.Methods.  We measured serum vitamin B12, folate, creatinine and albumin concentrations and plasma Hc concentrations in 101 consecutive patients with VTD, diagnosed by image tests and 101 control subjects, matched for age and sex.Results.  Serum vitamin B12 concentrations were significantly lower in VTD patients than in the control subjects. There were no differences in plasma Hc or serum folate concentrations between the groups. Among the male subgroup aged more than 70 years, serum vitamin B12 concentrations were significantly lower (240.88 ± 103.07 vs. 421.20 ± 314.31 pmol L−1; P = 0.03) and plasma Hc concentrations were significantly higher (13.1 ± 4.18 vs. 10.56 ± 3.06 μmol L−1; P =0.04) in VTD patients than in the control group. On multivariate analysis, in patients aged more than 70 years, serum vitamin B12 concentrations were independently associated with VTD. Compared with the highest quartile of vitamin B12 (>512.6 pmol L−1) the odds ratio (OR) for VTD in the lowest quartile (<230.9 pmol L−1) was 3.8 (95% CI 1.44–10.18; P = 0.01).In the VTD group, lowest vitamin B12 concentrations (percentile 10 <152.8 pmol L−1) were associated with the factor V Leiden mutation (OR = 6.07, 95% CI 0.93–38.55; P = 0.04).Conclusions.  Measuring vitamin B12 concentrations in elderly males may help in identifying people at risk of venous thromboembolism in our population.
Unwounded plants elicit Agrobacterium vir gene induction and T‐DNA transfer: transformed plant cells produce opines yet are tumour free
Authors: Brencic Anja , Angert Esther R. , Winans Stephen C. 
Published: August 2005

SummaryAgrobacterium tumefaciens is well known to cause crown gall tumours at plant wound sites and to benefit from this plant association by obtaining nutrients called opines that are produced by these tumours. Tumourigenesis requires expression of the vir regulon in response to chemical signals that are thought to be released from wound sites. Here, we examine chemical interactions between A. tumefaciens and unwounded plants. To determine whether unwounded plants can release significant amounts of vir gene inducers, we constructed an A. tumefaciens strain carrying a PvirB–gfp fusion. This fusion was strongly induced by co‐culture with tobacco seedlings that have been germinated without any intentional wounding. The release of phenolic vir gene inducers was confirmed by GC/MS analysis. We also constructed a strain containing the gfp reporter located on an artificial T‐DNA and expressed from a plant promoter. A. tumefaciens efficiently transferred this T‐DNA into cells of unwounded plants in the absence of exogenous vir gene inducers. Many cells of seedlings colonized by the bacteria also produced octopine, which was detected using a Pocc‐gfp reporter strain. This indicates transfer of the native T‐DNA. However, these transformed plant cells did not form tumours. These results suggest that successful colonization of plants by A. tumefaciens, including T‐DNA transfer and opine production, does not require wounding and does not necessarily cause cell proliferation. Transformation of plant cells without inciting tumours may represent a colonization strategy for this pathogen that has largely been overlooked.
Transcriptional regulation of flhDC by QseBC and σ 28 (FliA) in enterohaemorrhagic Escherichia coli
Authors: Clarke Marcie B. , Sperandio Vanessa 
Published: August 2005

SummaryEnterohaemorrhagic Escherichia coli (EHEC) serotype O157:H7, the causative agent of haemorrhagic colitis, has been shown to utilize a cell‐to‐cell signalling system to regulate gene expression. We have previously reported that the quorum sensing E. coli regulators B and C (QseBC) may act as a two‐component system in EHEC to transcriptionally regulate the expression of flagella and motility through flhDC, the master regulator of flagella and motility genes. Here, we performed deletion analyses using the flhDC promoter in order to determine the minimal promoter regions necessary for QseBC transcriptional activation. We also performed electrophoretic mobility shift assays, competition experiments and DNaseI footprints, which suggest that QseB directly binds the flhDC promoter at high‐ and low‐affinity binding sites. These analyses have allowed us to determine the potential consensus sequence to which QseB binds in order to regulate transcription. Additionally, we mapped the transcriptional start site of flhDC responsive to QseBC, leading to the identification of a conserved FliA (σ 28) consensus sequence. These results suggest that FliA (σ 28), a class 2 flagellar gene, may be aiding in the transcriptional initiation of class 1 genes (flhDC) in EHEC. In order to further characterize the role of FliA (σ 28) in transcription of the flhDC promoter, we constructed a fliA isogenic mutant in EHEC. The flhDC::lacZ transcriptional fusion showed decreased activity in the fliA mutant compared with wild‐type and complemented strains. Taken together, these results indicate that transcriptional initiation at the flhDC promoter by QseBC appears to be complex and dependent on the presence of FliA (σ 28).
Transposition is modulated by a diverse set of host factors in Escherichia coli and is stimulated by nutritional stress
Authors: Twiss Erin , Coros Abbie M. , Tavakoli Norma P. , Derbyshire Keith M. 
Published: August 2005

SummaryThe role of host factors in regulating bacterial transposition has never been comprehensively addressed, despite the potential consequences of transposition. Here, we describe a screen for host factors that influence transposition of IS903, and the effect of these mutations on two additional transposons, Tn10 and Tn552. Over 20 000 independent insertion mutants were screened in two strains of Escherichia coli; from these we isolated over 100 mutants that altered IS903 transposition. These included mutations that increased or decreased the extent of transposition and also altered the timing of transposition during colony growth. The large number of gene products affecting transposition, and their diverse functions, indicate that the overall process of transposition is modulated at many different steps and by a range of processes. Previous work has suggested that transposition is triggered by cellular stress. We describe two independent mutations that are in a gene required for fermentative metabolism during anaerobic growth, and that cause transposition to occur earlier than normal during colony development. The ability to suppress this phenotype by the addition of fumarate therefore provides direct evidence that transposition occurs in response to nutritional stress. Other mutations that altered transposition disrupted genes normally associated with DNA metabolism, intermediary metabolism, transport, cellular redox, protein folding and proteolysis and together these define a network of host proteins that could potentially allow readout of the cell's environmental and nutritional status. In summary, this work identifies a collection of proteins that allow the host to modulate transposition in response to cell stress.
Early life predictors of adolescent smoking: findings from the Mater‐University study of pregnancy and its outcomes
Authors: Lawlor Debbie A. , O'Callaghan Michael J. , Mamun Abdullah A. , Williams Gail M. , Bor William , Najman Jake M. 
Published: August 2005

SummaryIn this study we have examined the early life predictors of smoking at age 14 in a birth cohort of individuals born in Brisbane, Australia between 1981 and 1984. In stratified and multivariable analyses maternal smoking throughout pregnancy and when the child was aged 14 were both associated with the child smoking: fully adjusted odds ratio [95% confidence interval] comparing maternal smoking throughout pregnancy with never smoking was 1.40 [1.25, 1.65] and that comparing maternal smoking when the child was aged 14 with not smoking was 1.57 [1.19, 2.06]. The association of maternal smoking throughout pregnancy was specific for adolescent smoking and was not associated with alcohol consumption, TV viewing or self‐report of poor school performance at age 14. Maternal and paternal educational attainment were also associated with smoking at age 14, with these associations attenuating towards the null with adjustment for childhood behavioural problems and cognitive function. There was no association of family income with smoking at age 14 once other explanatory variables were taken into account.
A meta‐analysis of randomized control trials of progestational agents in pregnancy
Authors: GOLDSTEIN PETER , BERRIER JAYNE , ROSEN SCOTT , SACKS HENRY S. , CHALMERS THOMAS C. 
Published: August 2005

SummaryThe continued use of progestational agents in attempts to achieve a normal outcome of pregnancy in women with a ‘high‐risk’ pregnancy (previous miscarriage, stillbirth or present preterm labour) prompted this meta‐analysis of randomized control trials of such therapy. Of 20 trials of a progestogen 15 had combinable data. Combined comparisons, using odds ratios with confidence intervals, were made of the rates of livebirths at term or preterm and the sum of term and preterm deliveries, miscarriages, stillbirths and neonatal deaths. All but one comparison failed to show a significant benefit. Only the preterm delivery versus the term delivery comparison approached statistical significance. There were average deficiencies of quality apparent in the studies, and a test for heterogeneity among the studies was positive, but these caveats do not diminish the conclusion that progestogens should not be used outside of randomized trials at present. If trials are done, they should include only women with demonstrated hormonal abnormalities who are carrying a live fetus as shown by ultrasonography.
Unemployment and reproductive outcome. An Australian study
Authors: NAJMAN J. M. , MORRISON J. , WILLIAMS G. M. , KEEPING J. D. , ANDERSEN M. J. 
Published: August 2005

SummaryThe Mater‐University of Queensland Study involves the follow‐up of 8556 pregnant women who were enrolied at their first clinic visit. This analysis compares four groups of women categorized according to their own and their partners' employment Status. Group l comprised women unemployed, partners not unemployed. Group 2 comprised women not unemployed with unemployed partners. Group 3 comprised women and partners who were both unemployed. In group 4 ncither partner was unemployed. Initial analysis showed that there was a significant association between birthweight and birthweight for gestational age, and unemployment as reported by mothers. After adjustment for lifestyle variables (principally smoking) there were no remaining statistically significant associations.