Förderzeitraum 2017
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Institute
- Theodor-Boveri-Institut für Biowissenschaften (23)
- Institut für Klinische Epidemiologie und Biometrie (9)
- Institut für Psychologie (9)
- Abteilung für Molekulare Innere Medizin (in der Medizinischen Klinik und Poliklinik II) (8)
- Institut für Sportwissenschaft (8)
- Institut für Virologie und Immunbiologie (8)
- Neurologische Klinik und Poliklinik (8)
- Klinik und Poliklinik für Thorax-, Herz- u. Thorakale Gefäßchirurgie (7)
- Klinik und Poliklinik für Unfall-, Hand-, Plastische und Wiederherstellungschirurgie (Chirurgische Klinik II) (7)
- Medizinische Klinik und Poliklinik I (7)
Background:
Contrast-enhanced cardiovascular magnetic resonance angiography (CE-CMRA) is the established imaging modality for patients with Marfan syndrome requiring life-long annual aortic imaging before and after aortic root replacement. Contrast-free CMRA techniques avoiding side-effects of contrast media are highly desirable for serial imaging but have not been evaluated in the postoperative setup of Marfan patients. The purpose of this study was to assess the feasibility of non-contrast balanced steady-state free precession (bSSFP) magnetic resonance imaging for aortic monitoring of postoperative patients with Marfan syndrome.
Methods:
Sixty-four adult Marfan patients after aortic root replacement were prospectively included. Fourteen patients (22%) had a residual aortic dissection after surgical treatment of type A dissection. bSSFP imaging and CE-CMRA were performed at 1.5 Tesla. Two radiologists evaluated the images regarding image quality (1 = poor, 4 = excellent), artifacts (1 = severe, 4 = none) and aortic pathologies. Readers measured the aortic diameters at defined levels in both techniques. Statistics included observer agreement for image scoring and diameter measurements and ROC analyses for comparison of the diagnostic performance of bSSFP and CE-CMRA.
Results:
Both readers observed no significant differences in image quality between bSSFP and CE-CMRA and found a median image quality score of 4 for both techniques (all p > .05). No significant differences were found regarding the frequency of image artifacts in both sequences (all p > .05). Sensitivity and specificity for detection of aortic dissections was 100% for both readers and techniques. Compared to bSSFP imaging, CE-CMRA resulted in higher diameters (mean bias, 0.9 mm; p < .05). The inter-observer biases of diameter measurements were not significantly different (all p > .05), except for the distal graft anastomosis (p = .001). Using both techniques, the readers correctly identified a graft suture dehiscence with aneurysm formation requiring surgery.
Conclusion:
Unenhanced bSSFP CMR imaging allows for riskless aortic monitoring with high diagnostic accuracy in Marfan patients after aortic root surgery.
The highly motile and versatile protozoan pathogen Trypanosoma brucei undergoes a complex life cycle in the tsetse fly. Here we introduce the host insect as an expedient model environment for microswimmer research, as it allows examination of microbial motion within a diversified, secluded and yet microscopically tractable space. During their week-long journey through the different microenvironments of the fly´s interior organs, the incessantly swimming trypanosomes cross various barriers and confined surroundings, with concurrently occurring major changes of parasite cell architecture. Multicolour light sheet fluorescence microscopy provided information about tsetse tissue topology with unprecedented resolution and allowed the first 3D analysis of the infection process. High-speed fluorescence microscopy illuminated the versatile behaviour of trypanosome developmental stages, ranging from solitary motion and near-wall swimming to collective motility in synchronised swarms and in confinement. We correlate the microenvironments and trypanosome morphologies to high-speed motility data, which paves the way for cross-disciplinary microswimmer research in a naturally evolved environment.
Antinociceptive pathways are activated in the periphery in inflammatory pain, for instance resolvins and opioid peptides. Resolvins are biosynthesized from omega-3 polyunsaturated fatty acids such as eicosapentaenoic acid and docosahexaenoic acid. Resolvin D1 (RvD1) and resolvin E1 (RvE1) initiate the resolution of inflammation and control of hypersensitivity via induction of anti-inflammatory signaling cascades. RvD1 binds to lipoxin A4/annexin-A1 receptor/formyl-peptide receptor 2 (ALX/FPR2), RvE1 to chemerin receptor 23 (ChemR23). Antinociception of RvD1 is mediated by interaction with transient receptor potential channels ankyrin 1 (TRPA1). Endogenous opioid peptides are synthesized and released from leukocytes in the tissue and bind to opioid receptors on nociceptor terminals. Here, we further explored peripheral mechanisms of RvD1 and chemerin (Chem), the ligand of ChemR23, in complete Freund’s adjuvant (CFA)-induced hindpaw inflammation in male Wistar rats. RvD1 and Chem ameliorated CFA-induced hypersensitivity in early and late inflammatory phases. This was prevented by peripheral blockade of the μ-opioid peptide receptor (MOR) using low dose local naloxone or by local injection of anti-β-endorphin and anti-met-enkephalin (anti-ENK) antibodies. Naloxone also hindered antinociception by the TRPA1 inhibitor HC-030031. RvD1 did not stimulate the release of β-endorphin from macrophages and neutrophils, nor did RvD1 itself activate G-proteins coupled MOR or initiate β-arrestin recruitment to the membrane. TRPA1 blockade by HC-030031 in inflammation in vivo as well as inhibition of the TRPA1-mediated calcium influx in dorsal root ganglia neurons in vitro was hampered by naloxone. Peripheral application of naloxone alone in vivo already lowered mechanical nociceptive thresholds. Therefore, either a perturbation of the balance of endogenous pro- and antinociceptive mechanisms in early and late inflammation, or an interaction of TRPA1 and opioid receptors weaken the antinociceptive potency of RvD1 and TRPA1 blockers.
Natural enemies have been shown to be effective agents for controlling insect pests in crops. However, it remains unclear how different natural enemy guilds contribute to the regulation of pests and how this might be modulated by landscape context. In a field exclusion experiment in oilseed rape (OSR), we found that parasitoids and ground-dwelling predators acted in a complementary way to suppress pollen beetles, suggesting that pest control by multiple enemies attacking a pest during different periods of its occurrence in the field improves biological control efficacy. The density of pollen beetle significantly decreased with an increased proportion of non-crop habitats in the landscape. Parasitism had a strong effect on pollen beetle numbers in landscapes with a low or intermediate proportion of non-crop habitats, but not in complex landscapes. Our results underline the importance of different natural enemy guilds to pest regulation in crops, and demonstrate how biological control can be strengthened by complementarity among natural enemies. The optimization of natural pest control by adoption of specific management practices at local and landscape scales, such as establishing non-crop areas, low-impact tillage, and temporal crop rotation, could significantly reduce dependence on pesticides and foster yield stability through ecological intensification in agriculture.
Trypanosoma brucei is a protozoan flagellate that is transmitted by tsetse flies into the mammalian bloodstream. The parasite has a huge impact on human health both directly by causing African sleeping sickness and indirectly, by infecting domestic cattle. The biology of trypanosomes involves some highly unusual, nuclear-localised processes. These include polycistronic transcription without classical promoters initiated from regions defined by histone variants, trans-splicing of all transcripts to the exon of a spliced leader RNA, transcription of some very abundant proteins by RNA polymerase I and antigenic variation, a switch in expression of the cell surface protein variants that allows the parasite to resist the immune system of its mammalian host. Here, we provide the nuclear proteome of procyclic Trypanosoma brucei, the stage that resides within the tsetse fly midgut. We have performed quantitative label-free mass spectrometry to score 764 significantly nuclear enriched proteins in comparison to whole cell lysates. A comparison with proteomes of several experimentally characterised nuclear and non-nuclear structures and pathways confirmed the high quality of the dataset: the proteome contains about 80% of all nuclear proteins and less than 2% false positives. Using motif enrichment, we found the amino acid sequence KRxR present in a large number of nuclear proteins. KRxR is a sub-motif of a classical eukaryotic monopartite nuclear localisation signal and could be responsible for nuclear localization of proteins in Kinetoplastida species. As a proof of principle, we have confirmed the nuclear localisation of six proteins with previously unknown localisation by expressing eYFP fusion proteins. While proteome data of several T. brucei organelles have been published, our nuclear proteome closes an important gap in knowledge to study trypanosome biology, in particular nuclear-related processes.
The aim of the present study was to examine whether fostering positive activating affect during multimedia learning enhances learning outcome. University students were randomly assigned to either a multimedia learning environment designed to induce positive activating affect through the use of “warm” colours and rounded shapes () or an affectively neutral environment that used achromatic colours and sharp edges (). Participants learned about the topic of functional neuroanatomy for 20 minutes and had to answer several questions for comprehension and transfer afterwards. Affective states as well as achievement goal orientations were investigated before and after the learning phase using questionnaires. The results show that participants in the affectively positive environment were superior in comprehension as well as transfer when initial affect was strong. Preexperimental positive affect was therefore a predictor of comprehension and a moderator for transfer. Goal orientations did not influence these effects. The findings support the idea that positive affect, induced through the design of the particular multimedia learning environment, can facilitate performance if initial affective states are taken into account.
Phospholipids occurring in cell membranes and lipoproteins are converted into oxidized phospholipids (OxPL) by oxidative stress promoting atherosclerotic plaque formation. Here, OxPL were characterized as novel targets in acute and chronic inflammatory pain. Oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (OxPAPC) and its derivatives were identified in inflamed tissue by mass spectrometry and binding assays. They elicited calcium influx, hyperalgesia and induced pro-nociceptive peptide release. Genetic, pharmacological and mass spectrometric evidence in vivo as well as in vitro confirmed the role of transient receptor potential channels (TRPA1 and TRPV1) as OxPAPC targets. Treatment with the monoclonal antibody E06 or with apolipoprotein A-I mimetic peptide D-4F, capturing OxPAPC in atherosclerosis, prevented inflammatory hyperalgesia, and in vitro TRPA1 activation. Administration of D-4F or E06 to rats profoundly ameliorated mechanical hyperalgesia and inflammation in collagen-induced arthritis. These data reveal a clinically relevant role for OxPAPC in inflammation offering therapy for acute and chronic inflammatory pain treatment by scavenging OxPAPC.
An efficient multigrid finite-differences scheme for solving elliptic Fredholm partial integro-differential equations (PIDE) is discussed. This scheme combines a second-order accurate finite difference discretization of the PIDE problem with a multigrid scheme that includes a fast multilevel integration of the Fredholm operator allowing the fast solution of the PIDE problem. Theoretical estimates of second-order accuracy and results of local Fourier analysis of convergence of the proposed multigrid scheme are presented. Results of numerical experiments validate these estimates and demonstrate optimal computational complexity of the proposed framework.