Individualization of transfer function in estimation of central aortic pressure from the peripheral pulse is not required in patients at rest

Central aortic pressure gives better insight into ventriculo-arterial coupling and better prognosis of cardiovascular complications than peripheral pressures. Therefore transfer functions (TF), reconstructing aortic pressure from peripheral pressures, are of great interest. Generalized TFs (GTF) give useful results, especially in larger study populations, but detailed information on aortic pressure might be improved by individualization of the TF. We found earlier that the time delay, representing the travel time of the pressure wave between measurement site and aorta is the main determinant of the TF. Therefore, we hypothesized that the TF might be individualized (ITF) using this time delay. In a group of 50 patients at rest, aged 28-66 yr (43 men), undergoing diagnostic angiography, ascending aortic pressure was 119 +/- 20/70 +/- 9 mmHg (systolic/diastolic). Brachial pressure, almost simultaneously measured using catheter pullback, was 131 +/- 18/67 +/- 9 mmHg. We obtained brachial-to-aorta ITFs using time delays optimized for the individual and a GTF using averaged delay. With the use of ITFs, reconstructed aortic pressure was 121 +/- 19/69 +/- 9 mmHg and the root mean square error (RMSE), as measure of difference in wave shape, was 4.1 +/- 2.0 mmHg. With the use of the GTF, reconstructed pressure was 122 +/- 19/69 +/- 9 mmHg and RMSE 4.4 +/- 2.0 mmHg. The augmentation index (AI) of the measured aortic pressure was 26 +/- 13%, and with ITF and GTF the AIs were 28 +/- 12% and 30 +/- 11%, respectively. Details of the wave shape were reproduced slightly better with ITF but not significantly, thus individualization of pressure transfer is not effective in resting patients.     

Early events in preprotein recognition in E. coli: interaction of SRP and trigger factor with nascent polypeptides.

In Escherichia coli, components of a signal recognition particle (SRP) and its receptor have been identified which appear to be essential for efficient translocation of several proteins. In this study we use cross-linking to demonstrate that E. coli SRP interacts with a variety of nascent presecretory proteins and integral inner membrane proteins. Evidence is presented that the interaction is correlated with the hydrophobicity of the core region of the signal sequence and thereby with its ability to promote transport in vivo. A second E. coli component, which is identified as trigger factor, can be efficiently cross-linked to all tested nascent chains derived from both secreted and cytosolic proteins. We propose that SRP and trigger factor act as secretion-specific and general molecular chaperone respectively, early in protein synthesis.     

Induction of Adrenal Tyrosine Hydroxylase mRNA by Single Immobilization Stress Occurs Even After Splanchnic Transection and in the Presence of Cholinergic Antagonists

Abstract: Immobilization (IMO) stress elevates plasma catecholamines and increases tyrosine hydroxylase (TH) gene expression in rat adrenals. This study examined the mechanism(s) of IMO-induced changes in adrenal TH mRNA levels. Innervation of the adrenal medulla is predominantly cholinergic and splanchnicotomy as well as nicotinic receptor antagonists prevent the cold-induced rise in TH mRNA levels. In this study, the IMO-induced rise in plasma catecholamines, but not TH mRNA levels, was reduced by the antagonist chlorisondamine. Muscarinic antagonist atropine also did not prevent the IMO stress-elicited rise in TH mRNA. Furthermore, denervation of the adrenals by unilateral splanchnicotomy did not block the IMO-induced rise in TH mRNA but completely prevented the induction of neuropeptide Y mRNA. These results suggest that (1) the large increase in adrenal TH gene expression elicited by a single IMO stress is not regulated via cholinergic receptors or splanchnic innervation, and (2) there is a dissociation between regulatory mechanisms of catecholamine secretion and elevation of TH gene expression in the adrenal medulla of rats during IMO stress.     

Uptake and metabolism of enterolactone and enterodiol by human colon epithelial cells

The enterolignans enterolactone and enterodiol are phytoestrogens that are formed from plant lignans by microorganisms in the human colon. Enterolignans circulate in plasma as conjugates. We hypothesized that conjugation of enterolignans takes place in colon epithelial cells, and studied the time course of uptake and metabolism of enterolactone and enterodiol in three human colon epithelial cell lines. In addition, the conjugates were identified by mass spectrometry with accurate mass measurement (LC/QTOFMS/MS). Intracellular levels of conjugated enterolactone and enterodiol in HT29 cells rose immediately after starting the exposure. This was accompanied by a rapid decrease in free enterolactone and enterodiol in the exposure medium of HT29 and (un)differentiated CaCo-2 but not of CCD841CoTr cells. Conjugation and excretion of enterolactone and enterodiol was complete within 8 h, except for enterodiol in CaCo-2 cells ( approximately 48 h). Enterolactone appears to be more rapidly metabolized and/or excreted than enterodiol, and also the appearance of conjugated enterolactone in medium is less affected by the presence of enterodiol than vice versa. Total (free plus conjugated) enterolignan concentrations remained constant throughout the experiments. Three conjugates were identified in exposure medium of HT29 cells: enterolactone-sulfate, enterolactone-glucuronide, and enterodiol-glucuronide.Taken together, our data suggest that phase II metabolism of enterolactone and enterodiol already may take place during uptake in the colon and that colon epithelial cells may be responsible for this metabolism.     

Helicobacter acinonychis: genetic and rodent infection studies of a Helicobacter pylori-like gastric pathogen of cheetahs and other big cats

Insights into bacterium-host interactions and genome evolution can emerge from comparisons among related species. Here we studied Helicobacter acinonychis (formerly H. acinonyx), a species closely related to the human gastric pathogen Helicobacter pylori. Two groups of strains were identified by randomly amplified polymorphic DNA fingerprinting and gene sequencing: one group from six cheetahs in a U.S. zoo and two lions in a European circus, and the other group from a tiger and a lion-tiger hybrid in the same circus. PCR and DNA sequencing showed that each strain lacked the cag pathogenicity island and contained a degenerate vacuolating cytotoxin (vacA) gene. Analyses of nine other genes (glmM, recA, hp519, glr, cysS, ppa, flaB, flaA, and atpA) revealed a approximately 2% base substitution difference, on average, between the two H. acinonychis groups and a approximately 8% difference between these genes and their homologs in H. pylori reference strains such as 26695. H. acinonychis derivatives that could chronically infect mice were selected and were found to be capable of persistent mixed infection with certain H. pylori strains. Several variants, due variously to recombination or new mutation, were found after 2 months of mixed infection. H. acinonychis ' modest genetic distance from H. pylori, its ability to infect mice, and its ability to coexist and recombine with certain H. pylori strains in vivo should be useful in studies of Helicobacter infection and virulence mechanisms and studies of genome evolution.     

Inheritance mode of multiple sclerosis: the effect of <Emphasis Type="Italic">HLA</Emphasis> class II alleles is stronger than additive

We previously identified on chromosome 6 an interval of 51 kb as the most likely interval in the HLA region for a disease-susceptibility locus for multiple sclerosis (MS). The interval was located between markers G511525 and D6S1666 and identified by the haplotype sharing statistic (HSS). The study comprised 124 patients with ancestry within the northeastern part of the Netherlands. Haplotype clustering indicated that two different ancestral haplotypes likely include a polymorphism involved in susceptibility to MS. To investigate the dominance characteristics of the MS susceptibility locus in the HLA class II region, we reanalyzed our data, performing genotype association analyses for both marker loci separately and for the two-locus haplotype. The two-locus genotype association analysis showed that in individuals who carry only one of the risk haplotypes the risk for MS is moderately increased (odds ratio (OR) 2.82; 95% confidence interval (CI) 1.50–5.31). However, in individuals carrying two risk haplotypes the risk for MS is highly increased compared with individuals who carry no risk haplotypes (OR 37.00; 95% CI 8.31–164.74). This susceptibility locus for MS seems to follow an intermediate mode of inheritance. Fitting additive, multiplicative and third power risk models to the data, the effect appears to be significantly stronger than additive.     

Single amino acid variation in barley 14-3-3 proteins leads to functional isoform specificity in the regulation of nitrate reductase

The highly conserved family of 14-3-3 proteins function in the regulation of a wide variety of cellular processes. The presence of multiple 14-3-3 isoforms and the diversity of cellular processes regulated by 14-3-3 suggest functional isoform specificity of 14-3-3 isoforms in the regulation of target proteins. Indeed, several studies observed differences in affinity and functionality of 14-3-3 isoforms. However, the structural variation by which isoform specificity is accomplished remains unclear. Because other reports suggest that specificity is found in differential expression and availability of 14-3-3 isoforms, we used the nitrate reductase (NR) model system to analyse the availability and functionality of the three barley 14-3-3 isoforms. We found that 14-3-3C is unavailable in dark harvested barley leaf extract and 14-3-3A is functionally not capable to efficiently inhibit NR activity, leaving 14-3-3B as the only characterized isoform able to regulate NR in barley. Further, using site directed mutagenesis, we identified a single amino acid variation (Gly versus Ser) in loop 8 of the 14-3-3 proteins that plays an important role in the observed isoform specificity. Mutating the Gly residue of 14-3-3A to the alternative residue, as found in 14-3-3B and 14-3-3C, turned it into a potent inhibitor of NR activity. Using surface plasmon resonance, we show that the ability of 14-3-3A and the mutated version to inhibit NR activity correlates well with their binding affinity for the 14-3-3 binding motif in the NR protein, indicating involvement of this residue in ligand discrimination. These results suggest that both the availability of 14-3-3 isoforms as well as binding affinity determine isoform-specific regulation of NR activity.     

The microfood web of grassland soils responds to a moderate increase in atmospheric CO2

The response of the soil microfood web (microflora, nematodes) to a moderate increase in atmospheric CO₂ (+20%) was investigated by means of a free air CO₂ enrichment experiment. The study was carried out in a seminatural temperate grassland for a period of 4 consecutive years (1 year before fumigation commenced and 3 years with fumigation). Several soil biological parameters showed no change (microbial biomass, bacterial biomass) or decline (microbial respiration) in the first year of elevated CO₂ treatment as compared with controls. Each of these parameters were higher than controls, however, after 3 years of treatment. The relative abundance of predaceous nematodes also decreased in year 1 of the experiment, increased in year 2, but decreased again in year 3. In contrast, the relative abundance of root hair feeding nematodes, at first, increased under elevated CO₂ and then returned to the initial level again. Increased microbial biomass indicates enhanced C storage in the labile carbon pool of the active microfood web in subsequent years. According to measurements on the amounts of soil extractable C, changes in resource availability seem to be key to the response of the soil microfood web. We found a strong response of bacteria to elevated CO₂, while the fungal biomass remained largely unchanged. This contrasts to findings reported in the literature. We hypothesize that this may be because of contrasting effects of different levels of CO₂ enrichment on the microbial community (i.e. stimulation of bacteria at moderate levels and stimulation of fungi at high levels of CO₂ enrichment). However, various CO₂ effects observed in our study are similar in magnitude to those observed in other studies for a much higher level of atmospheric carbon. These include the particular sensitivity of predaceous nematodes and the long‐term increase of microbial respiration. Our findings confirm that the potential of terrestrial ecosystems to accumulate additional carbon might be lower than previously thought. Furthermore, CO₂‐induced changes of temperate grassland ecosystems might emerge much earlier than expected.     

The Ordinal Effects of Ostracism: A Meta-Analysis of 120 Cyberball Studies

We examined 120 Cyberball studies (N = 11,869) to determine the effect size of ostracism and conditions under which the effect may be reversed, eliminated, or small. Our analyses showed that (1) the average ostracism effect is large (d > |1.4|) and (2) generalizes across structural aspects (number of players, ostracism duration, number of tosses, type of needs scale), sampling aspects (gender, age, country), and types of dependent measure (interpersonal, intrapersonal, fundamental needs). Further, we test Williams’s (2009) proposition that the immediate impact of ostracism is resistant to moderation, but that moderation is more likely to be observed in delayed measures. Our findings suggest that (3) both first and last measures are susceptible to moderation and (4) time passed since being ostracized does not predict effect sizes of the last measure. Thus, support for this proposition is tenuous and we suggest modifications to the temporal need-threat model of ostracism.