Experimental approaches to understand the role of genetic and environmental influences on the microbial community associated with "Daphnia"

Every multicellular organism on this planet is associated with a diverse community of microorganisms referred to as its microbiota. In recent years, myriads of effects resulting from this interaction have been revealed. The series of experiments condensed in this thesis aimed at investigating this relationship in more detail in planktonic crustaceans from the genus Daphnia and in particular the water flea Daphnia magna. The findings from these experiments provide important basic knowledge essential for future host-microbiota related research in this system. Part one of the thesis comprises all experiments conducted by myself. In the first chapter I reciprocally transplanted the microbiota between the two species Daphnia magna and Daphnia pulex to examine the degree of specificity in these associations and determine the effects on host fitness as a consequence thereof. We found that being associated with a foreign microbial community did not negatively affect maturity, fecundity and size in both Daphnia species, letting us speculate that the two partners did not adapt to each other. This hypothesis was further supported by the insights gained when investigating the transmission of the whole microbial community, which was the purpose of the second chapter. Compositional comparisons between maternal and offspring microbiota revealed a stable fraction of microbes that gets transmitted, neither influenced by the origin nor the diversity of the microbial community. The third chapter of the thesis aimed at assessing the stability of the Daphnia-microbiota association and to what degree established microbial communities were still modifiable. We paired and raised juveniles from three different locations (Belgium, Germany and Switzerland) in a full factorial design and compared their microbiota. We found that the microbiota is easily modifiable and that microbial communities greatly influence each other’s composition. In addition, the results allowed the conclusion that the microbiota is not genetically controlled. We further investigated this in the fourth chapter dedicated to evaluate if the homozygosity level of the host influences microbial diversity by comparing the microbiota of selfed and outcrossed animals. From the results we conclude that the host genotype has little influence on the diversity of the microbiota. Taken together, these results suggest that although microbial communities play a crucial role in Daphnia, the two partners did not adapt to one another leading us to propose a scenario of how transmission in the Daphnia-microbiota association might take place. Part two of the thesis encompasses work resulting from collaborations. In chapter five, Alexandra Mushegian tested the role of bacteria for animal functioning, showing a positive effect on embryonic development under warm temperature conditions. The goal of the last chapter, conducted by Karen Sullam, was to investigate the effect of temperature, host clone, and their interaction on host-associated microbiota. The experiment showed that the interaction of the factors affected microbial community structure while their diversity was more affected by host clonal background

Clinical Applications for Cardiovascular Magnetic Resonance Imaging at 3 Tesla

Cardiovascular magnetic resonance (CMR) imaging has evolved rapidly and is now accepted as a powerful diagnostic tool with significant clinical and research applications. Clinical 3 Tesla (3 T) scanners are increasingly available and offer improved diagnostic capabilities compared to 1.5 T scanners for perfusion, viability, and coronary imaging. Although technical challenges remain for cardiac imaging at higher field strengths such as balanced steady state free precession (bSSFP) cine imaging, the majority of cardiac applications are feasible at 3 T with comparable or superior image quality to that of 1.5 T. This review will focus on the benefits and limitations of 3 T CMR for common clinical applications and examine areas in development for potential clinical use

Monitoring of Carboxypeptidase Digestion by Matrix-Assisted Laser Desorption and Ionization Mass Spectrometry

The potential of matrix-assisted laser desorption and ionization mass spectrometry (LDI-MS) is demonstrated by monitoring and analyzing the digestion of (human) pTH (1–34), a synthetic peptide with carboxypeptidases Y and B. All occurring ion signals in the mass spectra could be identified as degraded peptides. By calculating the mass differences between successive degraded peptides, it was possible to identify the released amino acids and to determine 8 amino acids of the C-terminus of the original peptide. For a single MS measurement, only 2 pmol of substrate was needed. Time-course analysis of the cleavage of the first amino acid residue gave insight into the kinetics involved. These measurements strongly support the hope that quantitative information about concentrations can be extracted from LDI-MS

Resource use and outcome in critically ill patients with hematological malignancy: a retrospective cohort study

INTRODUCTION: The paucity of data on resource use in critically ill patients with hematological malignancy and on these patients' perceived poor outcome can lead to uncertainty over the extent to which intensive care treatment is appropriate. The aim of the present study was to assess the amount of intensive care resources needed for, and the effect of treatment of, hemato-oncological patients in the intensive care unit (ICU) in comparison with a nononcological patient population with a similar degree of organ dysfunction. METHODS: A retrospective cohort study of 101 ICU admissions of 84 consecutive hemato-oncological patients and 3,808 ICU admissions of 3,478 nononcological patients over a period of 4 years was performed. RESULTS: As assessed by Therapeutic Intervention Scoring System points, resource use was higher in hemato-oncological patients than in nononcological patients (median (interquartile range), 214 (102 to 642) versus 95 (54 to 224), P < 0.0001). Severity of disease at ICU admission was a less important predictor of ICU resource use than necessity for specific treatment modalities. Hemato-oncological patients and nononcological patients with similar admission Simplified Acute Physiology Score scores had the same ICU mortality. In hemato-oncological patients, improvement of organ function within the first 48 hours of the ICU stay was the best predictor of 28-day survival. CONCLUSION: The presence of a hemato-oncological disease per se is associated with higher ICU resource use, but not with increased mortality. If withdrawal of treatment is considered, this decision should not be based on admission parameters but rather on the evolutional changes in organ dysfunctions

Self-assembly and two-dimensional spontaneous resolution of cyano-functionalized [7]helicenes on Cu111

Birds of a feather flock together: STM and DFT studies provide the first example of spontaneous chiral resolution of a helicene on a surface. Racemic 6,13-dicyano[7]helicene forms fully segregated domains of pure enantiomers (2D conglomerate) on Cu(111). The propensity of the system to optimize intermolecular CN⋅⋅⋅HC(Ar) hydrogen bonding and CN⋅⋅⋅CN dipolar interactions translates into chiral recognition with preferential assembly of homochiral molecules

Resource utilization for chimeric antigen receptor T cell therapy versus autologous hematopoietic cell transplantation in patients with B cell lymphoma

CD19-directed chimeric antigen receptor T cells (CAR-T) have emerged as a highly efficacious treatment for patients with relapsed/refractory (r/r) B cell lymphoma (BCL). The value of CAR-T for these patients is indisputable, but one-off production costs are high, and little is known about the ancillary resource consumption associated with CAR-T treatment. Here, we compared the resource use and costs of CAR-T treatment with high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) for patients with r/r BCL. Standard operating procedures were used to develop a process model in ClipMedPPM, which comprises all activities and processes to sustain or generate treatment components that together constitute a treatment path. The software allows a graphic representation and the use of standardized linguistic elements for comparison of different treatment paths. Detailed processes involved in CAR-T treatments (n = 1041 processes) and in ASCT (n = 1535) were analyzed for time consumption of treatment phases and personnel. Process costs were calculated using financial controlling data. CAR-T treatment required ~ 30% less staff time than ASCT (primarily nursing staff) due to fewer chemotherapy cycles, less outpatient visits, and shorter hospital stays. For CAR-T, production costs were ~ 8 × higher, but overall treatment time was shorter compared with ASCT (30 vs 48 days), and direct labor and overhead costs were 40% and 10% lower, respectively. Excluding high product costs, CAR-T uses fewer hospital resources than ASCT for r/r BCL. Fewer hospital days for CAR-T compared to ASCT treatment and the conservation of hospital resources are beneficial to patients and the healthcare system. Keywords: Aggressive B cell lymphoma; Autologous stem cell transplantation (ASCT); Chimeric antigen receptor T cells (CAR-T); Comparative cost analysis; Health care resource consumptio