Rare Bisindole Alkaloids from the Amazonian Tree Raputia simulans

The stem bark of Raputia simulans (Rutaceae) has been reported to contain simple and dimeric indole alkaloids. Further phytochemical investigation of R. simulans stem bark resulted in the isolation of three new alkaloids. These compounds represent a relatively new category of dimeric indole alkaloids with a cyclohexene moiety in their core. Their structure elucidations were based on NMR and HR‐MS techniques, while structural aspects concerning their relative configuration were investigated using molecular mechanics calculations and NOESY experiments.     

Experimental verification of regression to the mean in redox biology: differential responses to exercise

An important methodological threat when selecting individuals based on initial values for a given trait is the “regression to the mean” artifact. This artifact appears when a group with an extreme mean value during a first measurement tends to obtain a less extreme value (i.e. tends toward the mean) on a subsequent measurement. The main aim was to experimentally confirm the presence of this artifact in the responses of the reference oxidative stress biomarker (F₂-isoprostanes) after exercise. Urine samples were collected before and immediately following acute exercise in order to determine the level of exercise-induced oxidative stress. Afterwards, participants were arranged into three groups based on their levels of exercise-induced oxidative stress (low, moderate and high oxidative stress groups; n?=?12 per group). In order to verify the existence of the regression to the mean artifact, the three groups were subjected to a second exercise trial one week after the first trial. This study confirmed the regression to the mean artifact in a redox biology context and showed that this artifact can be minimized by performing a duplicate pretreatment measurement after completing a nonrandom sorting based on the first assessment. This study also indicated that different individuals experience high oxidative stress or reductive stress (or no stress) to the same exercise stimulus even after adjusting for regression to the mean. This finding substantiates the methodological choice to divide individuals based on their degree of exercise-induced oxidative stress in future experiments to investigate the role of reactive species in exercise adaptations.     

Development and preliminary validation of Brace Questionnaire (BrQ): a new instrument for measuring quality of life of brace treated scoliotics

Background

The effectiveness of orthotic treatment continues to be controversial in international medical literature due to differences in the reported results and conclusions of various studies. Heterogeneity of the samples has been suggested as a reason for conflicting results. Besides the obvious theoretical differences between the brace concepts, the variability in the technical factors can also explain the contradictory results between same brace types. This paper will investigate the degree of variability among responses of scoliosis specialists from the Brace Study Ground of the International Society on Scoliosis Orthopedic and Rehabilitation Treatment SOSORT. Ultimately, this information could be a foundation for establishing a consensus and framework for future prospective controlled studies.

Methods

A preliminary questionnaire on the topic of 'brace action' relative to the theory of three-dimensional scoliosis correction and brace treatment was developed and circulated to specialists interested in the conservative treatment of adolescent idiopathic scoliosis. A particular case was presented (main thoracic curve with minor lumbar). Several key points emerged and were used to develop a second questionnaire which was discussed and full filed after the SOSORT consensus meeting (Milano, Italy, January 2005).

Results

Twenty-one questionnaires were completed. The Chêneau brace was the most frequently recommended. The importance of the three point system mechanism was stressed. Options about proper pad placement on the thoracic convexity were divided 50% for the pad reaching or involving the apical vertebra and 50% for the pad acting caudal to the apical vertebra. There was agreement about the direction of the vector force, 85% selecting a 'dorso lateral to ventro medial' direction but about the shape of the pad to produce such a force. Principles related to three-dimensional correction achieved high consensus (80%–85%), but suggested methods of correction were quite diverse.

Conclusion

This study reveals that among participating SOSORT specialists there continues to be a strongly held and conflicting if not a contentious opinion regarding brace design and treatment. If the goal of a 'treatment consensus' is realistic and achievable, significantly more effort will be required to reconcile these differences.     

Downregulation by a long-acting beta2-adrenergic receptor agonist and corticosteroid of Staphylococcus aureus-induced airway epithelial inflammatory mediator production

Although Staphylococcus aureus is a major cause of pulmonary infection, the role played by this bacterium in the induction of inflammation of human airway epithelial cells (HAEC) is poorly understood. In this study, we investigated the inflammatory response of HAEC to S. aureus soluble virulence factors and demonstrate that the combination of a long-acting beta2-adrenergic receptor agonist (salmeterol) with a glucocorticoid (fluticasone propionate) has an anti-inflammatory effect on HAEC. First, we demonstrate increased expression at both the mRNA and protein levels of interleukin (IL)-8, IL-6, and tumor necrosis factor (TNF)-alpha following incubation of HAEC in the presence of S. aureus soluble virulence factors and the increase of 1) the free nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) activities and 2) the phosphorylated (P-) extracellular signal-regulated kinases 1 and 2 (ERK1/ERK2), the P-c-Jun NH2-terminal kinase (JNK), and the P-isoform-alpha of the NF-kappaB inhibitor (IkappaB alpha). Next, when HAEC were preincubated with the combination of salmeterol and fluticasone propionate, the inflammatory response of HAEC was markedly attenuated in that levels of IL-8, IL-6, TNF-alpha, NF-kappaB, AP-1, P-ERK1/ERK2, P-JNK, and P-IkappaB alpha decreased significantly. These data emphasize the deleterious effect of S. aureus soluble virulence factors and suggest that the combination of a beta2-adrenergic receptor agonist with a glucocorticoid may attenuate the associated airway epithelial inflammation.     

Estimation of the diagnostic threshold accounting for decision costs and sampling uncertainty

Medical diagnostic tests are used to classify subjects as non-diseased or diseased. The classification rule usually consists of classifying subjects using the values of a continuous marker that is dichotomised by means of a threshold. Here, the optimum threshold estimate is found by minimising a cost function that accounts for both decision costs and sampling uncertainty. The cost function is optimised either analytically in a normal distribution setting or empirically in a free-distribution setting when the underlying probability distributions of diseased and non-diseased subjects are unknown. Inference of the threshold estimates is based on approximate analytically standard errors and bootstrap-based approaches. The performance of the proposed methodology is assessed by means of a simulation study, and the sample size required for a given confidence interval precision and sample size ratio is also calculated. Finally, a case example based on previously published data concerning the diagnosis of Alzheimer's patients is provided in order to illustrate the procedure.     

Growing functional modules from a seed protein via integration of protein interaction and gene expression data

Background  

Nowadays modern biology aims at unravelling the strands of complex biological structures such as the protein-protein interaction (PPI) networks. A key concept in the organization of PPI networks is the existence of dense subnetworks (functional modules) in them. In recent approaches clustering algorithms were applied at these networks and the resulting subnetworks were evaluated by estimating the coverage of well-established protein complexes they contained. However, most of these algorithms elaborate on an unweighted graph structure which in turn fails to elevate those interactions that would contribute to the construction of biologically more valid and coherent functional modules.     

Baboons (Papio anubis) living in larger social groups have bigger brains

The evolutionary origin of Primates' exceptionally large brains is still highly debated. Two competing explanations have received much support: the ecological hypothesis and the social brain hypothesis (SBH). We tested the SBH in (n = 82) baboons (Papio anubis) belonging to the same research centre but housed in groups with size ranging from 2 to 63 individuals. We found that baboons living in larger social groups had larger brains. This effect was driven mainly by white matter volume and to a lesser extent by grey matter volume but not by the cerebrospinal fluid. In comparison, the size of the enclosure, an ecological variable, had no such effect. In contrast to the current re-emphasis on potential ecological drivers of primate brain evolution, the present study provides renewed support for the social brain hypothesis and suggests that the social brain plastically responds to group size. Many factors may well influence brain size, yet accumulating evidence suggests that the complexity of social life might be an important determinant of brain size in primates.