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101.
Workers of three ant species (Lasius niger, Lasius flavus, Myrmica rubra) were caged in the laboratory together with caterpillars and pupae of five species of lycaenid butterflies. Mortality of ants was 3–5 times higher when the ants were confined with larvae lacking a dorsal nectar organ (Lycaena phlaeas, Lycaena tityrus) rather than with caterpillars which possess a nectar gland (Aricia agestis, Polyommatus bellargus, P. icarus). For all five species, ant survival was always lower at the pupal stage (where a nectar organ is always absent) than at the caterpillar stage and was largely equivalent for the butterfly species tested. The experimental data confirm earlier estimates that ants can derive nutritive benefits from tending facultatively myrmecophilous lycaenid caterpillars, even though these caterpillars produce nectarlike secretions at low rates.  相似文献   
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Introduction

The immunosuppressive therapy with everolimus (ERL) after heart transplantation is characterized by a narrow therapeutic window and a substantial variability in dose requirement. Factors explaining this variability are largely unknown.

Objectives

Our aim was to evaluate factors affecting ERL metabolism and to identify novel metabolites associated with the individual ERL dose requirement to elucidate mechanisms underlying ERL dose response variability.

Method

We used liquid chromatography coupled with mass spectrometry for quantification of ERL metabolites in 41 heart transplant patients and evaluated the effect of clinical and genetic factors on ERL pharmacokinetics. Non-targeted plasma metabolic profiling by ultra-performance liquid chromatography and high resolution quadrupole-time-of-flight mass spectrometry was used to identify novel metabolites associated with ERL dose requirement.

Results

The determination of ERL metabolites revealed differences in metabolite patterns that were independent from clinical or genetic factors. Whereas higher ERL dose requirement was associated with co-administration of sodium-mycophenolic acid and the CYP3A5 expressor genotype, lower dose was required for patients receiving vitamin K antagonists. Global metabolic profiling revealed several novel metabolites associated with ERL dose requirement. One of them was identified as lysophosphatidylcholine (lysoPC) (16:0/0:0). Subsequent targeted analysis revealed that high levels of several lysoPCs were significantly associated with higher ERL dose requirement.

Conclusion

For the first time, this study describes distinct ERL metabolite patterns in heart transplant patients and detected potentially new drug–drug interactions. The global metabolic profiling facilitated the discovery of novel metabolites associated with ERL dose requirement that might represent new clinically valuable biomarkers to guide ERL therapy.
  相似文献   
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Background

Effective therapy of Acute Lung Injury (ALI) is still a major scientific and clinical problem. To define novel therapeutic strategies for sequelae of blunt chest trauma (TxT) like ALI/Acute Respiratory Distress Syndrome, we have investigated the immunomodulatory and regenerative effects of a single dose of ex vivo expanded human or rat mesenchymal stromal cells (hMSCs/rMSCs) with or without priming, immediately after the induction of TxT in Wistar rats.

Methods

We analyzed the histological score of lung injury, the cell count of the broncho alveolar lavage fluid (BAL), the change in local and systemic cytokine level and the recovery of the administered cells 24?h and 5 days post trauma.

Results

The treatment with hMSCs reduced the injury score 24?h after trauma by at least 50% compared with TxT rats without MSCs. In general, TxT rats treated with hMSCs exhibited a lower level of pro-inflammatory cytokines (interleukin [IL]-1B, IL-6) and chemokines (C-X-C motif chemokine ligand 1 [CXCL1], C-C motif chemokine ligand 2 [CCL2]), but a higher tumor necrosis factor alpha induced protein 6 (TNFAIP6) level in the BAL compared with TxT rats after 24?h. Five days after trauma, cytokine levels and the distribution of inflammatory cells were similar to sham rats. In contrast, the treatment with rMSCs did not reveal such therapeutic effects on the injury score and cytokine levels, except for TNFAIP6 level.

Conclusion

TxT represents a suitable model to study effects of MSCs as an acute treatment strategy after trauma. However, the source of MSCs has to be carefully considered in the design of future studies.  相似文献   
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Background

Students’ knowledge of scientific principles of evolution is often inadequate, despite its recognized importance for understanding biology. Moreover, difficulties associated with underlying abstract concepts such as randomness and probability can hinder successful learning of evolutionary concepts. Studies show that visualizations, particularly simulations together with appropriate instructional support, facilitate the learning of abstract concepts. Therefore, we have developed interactive, web-based simulation software called EvoSketch in efforts to help learners grasp the nature and importance of random and probabilistic processes in evolutionary contexts. We applied EvoSketch in an intervention study comparing four self-directed study conditions: learning with EvoSketch (1) alone, (2) combined with interpretative support, (3) combined with reflective support, and (4) using texts about randomness and probability instead of EvoSketch. All conditions received no support from any instructors. Knowledge about evolution as well as randomness and probability in the context of evolution, time-on-task, and perceived cognitive load were measured. A sample of 269 German secondary school students (Mage?=?15.6 years, SD?=?0.6 years) participated in the study.

Results

Learners using EvoSketch without additional support obtained higher follow-up test scores regarding their knowledge of randomness and probability than those using the text-based approach. However, use of the simulations together with given instructional support (interpretative or reflective) did not increase students’ performance, relative to the text-based approach. In addition, no significant between-intervention differences were found concerning the knowledge of evolution, while significant differences between the groups were detected concerning students’ perceived cognitive load and time-on-task.

Conclusions

From our findings, we conclude that EvoSketch seems to have a very small positive effect on students’ understanding of randomness and probability. Contrary to our expectations, additional self-directed instructional support did not improve students’ understanding, probably because it was not necessary to understand EvoSketch simulations. When using EvoSketch in the classroom, we recommend increasing the intervention timeframe to several sessions and a variety of evolutionary examples for which EvoSketch serves as an underlying framework.
  相似文献   
107.
Intrauterine growth restriction (IUGR) remains a major problem in perinatal medicine because of the variety of its underlying causes and the prediction of its outcome. Characteristics of heartbeat interval patterns are associated with neuro-vegetative and humoral regulatory processes. Fetal magnetocardiography allows non-invasive assessment of these processes with high precision throughout the second half of gestation. The aim of our study was the analysis of linear and non-linear parameters of fetal heart rate fluctuations to distinguish between IUGR fetuses and a cohort of normal subjects, both pre-selected from heart-rate traces representing a quiet state of activity in the third trimester of gestation.  相似文献   
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