Children as consumers in the food market : Empirical analyses investigating industry advertising self-regulation, children’s preferences, and purchasing behavior

In modern society, children have emerged as an important consumer demographic in the food market as they hold considerable purchasing power resulting from both their influence on family expenditures and their autonomous purchasing decisions. The food industry employs various marketing strategies to attract children’s attention and increase sales. However, due to their limited cognitive abilities, children are less capable to recognize the underlying purpose of such promotional activities, making them particularly vulnerable to these marketing strategies. Food-related marketing focuses primarily on highly processed food and beverage products that contain high levels of saturated fats, trans-fatty acids, added sugars, or salt (HFSS), potentially contributing to an obesogenic environment and childhood obesity. Based on the conceptual framework derived within this dissertation by synthesizing theoretical perspectives on consumer behavior, four empirical analyses are conducted, each focusing on selected aspects and determinants. The research aims to improve the understanding of children as independent consumers in the food market and determine behavioral, environmental, and personal factors that influence children’s responses to HFSS food marketing. This knowledge is essential for the development of policy interventions and consumer protection measures that promote healthier dietary choices among children. The first contribution of this dissertation investigates the effectiveness of the EU Pledge, a self-regulatory initiative launched by leading food and beverage companies in the EU. By focusing on Germany, it analyzes the impact on reducing children’s exposure to HFSS food and beverage television advertising. The results indicate limited effectiveness of the commitment due to the Pledges’s restriction on children’s programming and the relatively lenient nutritional criteria agreed on by signatory companies. The second study determines the impact of child-oriented on-product communication on children’s product preferences and investigates whether child-oriented food cues on packaging create a halo effect, improving the overall impression of taste and leading to a preference for the associated product. The findings suggest that positive impressions of packaging can support taste perception and product preference. The third research paper investigates primary school children’s autonomous snack purchasing decisions, considering the role of price and brand in influencing their spending on (un)healthy snacks by accounting for child-specific characteristics. The study findings highlight the heterogeneity of children as autonomous consumers in the snack market, with implications for their snack choice and price responsiveness. The fourth contribution focuses on the role of peer models on children’s independent snack purchasing decisions. The results emphasize that children tend to conform to their peer’s decisions, revealing the significant relevance of social influence in shaping children’s decision-making processes. Overall, the findings of the dissertation provide valuable insights that enhance the understanding of children as consumers in the food market and highlight the need for a comprehensive approach to improving the food environment of children. The dissertation draws revealing conclusions and implications for consumer policy aimed at promoting healthier food choices among children, and offers suggestions for future research in this domain

Impact of dietary interventions on metabolism and the gut-brain axis in adults with metabolic syndrome traits

In recent decades, the incidence of obesity and obesity-associated comorbidities such as the metabolic syndrome has exponentially increased in both developed and developing counties. It is widely accepted that inadequate dietary intake, especially a high consumption of ultra-processed, energy-dense foods and sugar-sweetened beverages, which is defined as ‘Western-type’ dietary pattern, is a main contributor to this global development. The Western-type dietary pattern encourages hyperenergetic nutrition leading to weight gain and increased visceral adipose tissue accumulation, which can result in subclinical, systemic inflammation and whole body insulin resistance. Moreover, the Western-type diet has been associated with a dysbiosis of the gut microbiota and age-related cognitive decline and dementia including Alzheimer’s diseases (AD) in epidemiological studies. The aim of this randomized, controlled intervention trial in obese adults with a habitual Western-type diet is to determine the effects of acute and mid-term, potentially health-promoting, dietary interventions on metabolic functions and brain health elucidating underlying mechanisms. One hundred and twenty obese, cognitively unimpaired adults aged 45 to 70 years with at least one metabolic syndrome trait including visceral fat distribution, (pre)hypertension, dyslipidemia, and a subclinical inflammation underwent a three hours mixed meal tolerance test (MMTT) for deep metabolic characterization. Fasting and multiple postprandial blood samples were collected to follow the time course of serum/plasma levels of insulin, glucose, blood lipids ((non)-LDL cholesterol, non-esterified fatty acids, and triglycerides), the gut hormone glucagon-like peptide 1 (GLP 1) and AD-related proteins (neurofilament light, glial fibrillary acidic protein, amyloid-beta 42/40, phosphorylated (phospho) tau 181 and 231, total-tau). Furthermore, genetic make-up, gut microbiome composition, and fecal microbial metabolites were analyzed. After completing the baseline visit, participants were randomly assigned to one of three study groups: the Nordic diet (ND) group, the lacto-ovo vegetarian diet (VD) group, or the control group (HD). The key components of the ND were berries, green leafy and root vegetables, whole grain from rye, spelt and oat, boiled potatoes, nuts, fish, and rapeseed oil. The VD comprised plant-derived foods complemented milk(products) and eggs. Both intervention diets were designed isoenergetically to ensure a constant body weight during the six weeks study period and were self-prepared by the participants according to detailed recipes. The HD group was instructed to maintain their habitual Western-type diet, physical activity level and body weight over the six weeks study duration. Compliance with the treatment was monitored using six weeks food diaries and a short-form questionnaire to review the frequency of consuming the key food items of the respective study diet as well as anthropometrics and several blood biomarkers as the fatty acids composition of the phospholipids or vitamin levels. After six weeks of dietary intervention, metabolite and microbiome analyses were repeated. After six weeks of ND intervention, significant reductions in the concentrations of LDL- and non-LDL cholesterol fractions as well as triglycerides and liver enzymes were observed. Both the ND and VD study diet induced taxonomic alterations of the gut microbiome. Correlation analysis of metabolic markers (lipid metabolism and liver enzymes) and the individual microbes revealed more than 80 significant correlations before and after intervention, suggesting a possible involvement of specific microbes in metabolism and outcome measures of the dietary intervention. The success of the ND in reducing blood lipids was determined by the basal gut microbiota composition, as the largest diet-induced reductions were seen in individuals with a specific microbiome signature. Furthermore, it was observed that individuals with the highest genetic risk for dyslipidemia benefited the most from the ND intervention. In fasting and postprandial levels of GLP-1, glucose, insulin, and AD-related protein concentrations, no ND- or VD induced effects were found. However, poorer long-term glucose control and higher fasting plasma glucose levels were associated with higher fasting and postprandial plasma (phospho) tau levels. The consumption of the standardized meal (MMTT) led to immediate changes in AD-related protein concentrations, which exceeded biomarker dynamics observed in the fasting state and were directly attributed to food intake and associated metabolic events. We concluded that specific microbial signatures and the individual genetic risk have a strong impact on the success of a dietary change, pointing towards a personalized nutrition approach in preventing cardiometabolic diseases. Because of the observed beneficial effects of the ND study diet on blood lipid profile and liver function, we concluded that the ND was superior to VD in reducing cardiometabolic risk factors. As both study diets were applied isoenergetically, the observed findings can directly be attributed to the specific key foods and nutrient profile of the respective dietary pattern. Furthermore, it was convincingly shown that food intake and glucose control have a decisive impact on the concentration of AD-related biomarkers, which should be considered when using these biomarkers for diagnosis and monitoring of disease progression and drug respons

Effektivität der selektiven internen Radiotherapie in Abhängigkeit von der Lokalisation des Primärtumors bei hepatisch metastasiertem kolorektalem Karzinom

Ziele Die Seite des Primärtumors erweist sich zunehmend als einer der wichtigsten Prognosefaktoren für Patienten mit metastasiertem Kolorektalkarzinom (mCRC). In der Vergangenheit wurde ein signifikanter Überlebensvorteil bei Patienten mit rechtsseitigem Primärtumor (RSP) nach selektiver interner Strahlentherapie (SIRT) plus mFOLFOX6-Chemotherapie (Folinsäure [Leucovorin], 5-Fluorouracil, Oxaliplatin) als Erstlinienbehandlung gegenüber der Chemotherapie allein beschrieben. Andere Studien kamen jedoch zu gegenteiligen Ergebnissen. Auf der Grundlage dieser Ergebnisse soll hier die Patientengruppe ermittelt werden, die am ehesten von einer SIRT profitieren würde. Material und Methoden: Retrospektiv wurden die Daten von 140 palliativen Darmkrebs-Patienten ausgewertet, die eine SIRT als letzte Therapieoption erhielten. Zum Vergleich der Überlebenszeiten wurde die Studie von Gibbs et al. herangezogen. Das Überleben wurde für zwei verschiedene Zeitpunkte ermittelt: OS.1 wurde vom Zeitpunkt der Erstdiagnose bis zum Todesdatum (n=136) oder dem letzten Untersuchungstermin definiert und OS.2 vom Beginn der SIRT Therapie bis zum Todesdatum oder dem letzten Untersuchungstermin (n=140). Die Wirksamkeit der SIRT wurde anhand der Kaplan-Maier-Überlebensanalyse und des Log-Rank-Tests bewertet. Patientenmerkmale, die für das Überleben relevant sein könnten, wurden ebenfalls erfasst und ausgewertet. Diese wurden mithilfe der uni- und multivariablen Cox-Regression analysiert. Das progressionsfreie Überleben wurde von der ersten SIRT bis zum ersten Nachweis einer intrahepatischen Progression durch CT oder MRT berechnet. Ergebnisse: Das Gesamtüberleben (OS) wurde für zwei verschiedene Zeitpunkte definiert. Zum einen, um die Ergebnisse mit früheren Studien vergleichen zu können (OS.1), und zum anderen, um den eigentlichen SIRT-Therapiezeitraum (OS.2) gesondert betrachten zu können. Das mediane OS.1 unserer Population betrug 39,0 Monate für LSP und 23,0 Monate für RSP (p Zusammenfassung: Es konnten verschiedene Patientenmerkmale definiert werden, die das Gesamtüberleben beeinflussen. Insbesondere das Vorhandensein einer K-RAS-Mutation und eines rechtsseitig lokalisierten Primärtumors erwies sich als negativer prognostischer Faktor für beide Gesamtüberlebensraten (OS.1 und OS.2). Nach dem Vergleich unserer Überlebensraten von SIRT als Last-Line-Therapie mit denen von Gibbs als First-Line-Therapie bei RSP-Patienten haben wir festgestellt, dass SIRT sowohl als First-Line- als auch als Last-Line-Therapie eingesetzt werden kann, um ein ähnlich langes Gesamtüberleben zu erreichen. Dagegen wurde ein Überlebensvorteil für LSP-Patienten nr dann festgestellt, wenn sie SIRT erst nach der Chemotherapie, d. h. als Last-Line-Therapie, erhielten. Somit konnte für beide Kollektive (RSP, LSP) eine positive Korrelation in Bezug auf das Gesamtüberleben bei Einsatz von SIRT als Last-Line-Therapie nachgewiesen werden.Aim: The primary tumor side is emerging as one of the main prognostic factors for patients with metastatic colorectal cancer (mCRC). Previously, a significant survival benefit was described in patients with right-sided primary (RSP) tumors after selective internal radiation therapy (SIRT) plus mFOLFOX6 (folinic acid [leucovorin], 5-fluorouracil, oxaliplatin) chemotherapy as a first-line treatment, versus chemotherapy alone. However, contrary results were provided by other studies. Based on these results, we here aim to identify the patient group, who is most likely to profit from a SIRT alone, administered as last line treatment. Materials and Methods: Retrospectively, data from 140 palliative CRC patients who received SIRT as the last therapy option were evaluated. The study by Gibbs et al was used to compare survival times. The survival was determined for two different points in time: OS.1 was defined from the time of the initial diagnosis to the date of death (n=136) or the last date of examination and OS.2 from the start of therapy with SIRT until the date of death or the last date of examination (n=140). The effectiveness of SIRT was evaluated using Kaplan Maier survival analysis and the log rank test. Patient characteristics that may be relevant for survival were also recorded and evaluated. These were analyzed using uni- and multivariable Cox regression. The progression free survival was calculated from first SIRT to the first evidence of intrahepatic progression detected by CT or MRT. Results: The OS was designed for two different points in time, first to compare the results with previous studies (OS.1) and second to view the actual SIRT therapy period separately (OS.2) The median OS.1 of our population was 39.0 months for LSP and 23.0 months for RSP (p < 0.001) with n=136, of which n=20 were censored patients. This shows a significantly longer survival than in the control group of Gibbs which was not treated with SIRT and equally defined from the time of initial diagnosis until death: LSP 26,6 months and RSP 17.1 months (p < 0.001). The median OS.2 of our population was 7.0 months for LSP and 4.0 months for RSP (p < 0.004) with n=140, of which n=20 were censored patients. The median progression-free survival was 3.0 months for LSP patients and 1.6 months for RSP patients (p < 0.032). Conclusion: Different patient’s characteristics influencing OS.1 and OS.2 could be defined. In particular the presence of a K-RAS mutation and a right-sided localized primary tumor proved to be a negative prognostic factor for both overall survivals. After comparing our survival rates of SIRT as a last-line therapy with those of Gibbs as a first-line therapy in RSP patients, we found that SIRT can be used as both first-line and last-line therapy for a similarly prolonged OS. Whereas a survival advantage was found for LSP patients if they received SIRT only after chemotherapy i.e. as last-line therapy. Therefor a positive correlation, in terms of overall survival, could be demonstrated using SIRT as a last line therapy in both collectives (RSP, LSP)

Multi-layer single-cell omics applications in the context of infection

Single cell multi-omics sequencing techniques have seen rapid developments in the last few years. The ability of pairing different data modalities makes it an attractive tool for investigating adaptive immune responses. This thesis consists of three projects, which share the common goal of gaining comprehensive insight into T cell biology through single cell multi-omics approaches. Initially, in this thesis I review major developments in the capture of single cell adaptive immune receptor repertoires (AIRR) in parallel with other single cell omics modalities. In addition, I summarise work conducted over four years to establish a framework for generating and analysing paired single cell RNA- and AIRR-sequencing data using single cell techniques available in our department. Building on this, we developed a comprehensive workflow to collect multi-omics single-cell data using the BD Rhapsody platform. This included whole transcriptome, cell surface markers (targeted sequencing-based cell surface proteomics), T cell specificities, AIRR profiles and sample multiplexing. With this technique I identified novel paired T-cell receptor sequences for three prominent HCMV epitopes. In addition, I review the ability of dCODE Dextramers to detect antigen-specific T cells at low frequencies by estimating sensitivities and specificities when used as sequencing reagents. In the final chapter of this thesis, we examine the kinetics of genome-wide changes in gene expression and chromatin accessibility, as well as temporal dynamics of transcription factor (TF) regulation early after Influenza A infection. We do this by tracking transgenic OT-I CD8+ T cells through the first divisions early after infection with recombinant Influenza A/Hong Kong/x31-OVA257-264 virus. We found that type I interferons served as an initial inflammatory trigger in undivided T cells, which instigated chromatin remodelling in genomic regions associated with TCR activation. Our chromatin accessibility data suggests that this happens in an IRF1 dependent manner. Remarkably, IFN-I signalling in undivided T cells was temporally limited. Upon antigen encounter, major chromatin restructuring occurred in undivided T cells, with SMARCC1 as a putative transcriptional regulator. For cells transitioning into the division phase, the positive TF regulators BATF and BATF3 were identified, aligning with their established roles in early effector differentiation. In a broader context, these findings offer a comprehensive view of how transcription factors govern gene expression during the initial cell divisions following infection, serving as a valuable resource for future investigations into early fate decisions of CD8+ T cells. In summary, the emerging field of multi-layer single-cell omics is set to reshape our understanding of adaptive immune responses by providing unprecedented insight into cellular heterogeneity, differentiation, and function. The work presented here demonstrates practical applications of these technologies and highlights their potential to transform the study of adaptive immunity in the future

Control of pulmonary immunity by physical exercise

Sedentary lifestyles combined with high caloric nutrition are widely known to severely contribute to the rise of metabolic diseases like diabetes, atherosclerosis, or obesity in recent years. While endurance training has been shown to induce the secretion of adipokines, and so-called myokines (muscle-derived cytokines), the impact of physical exercise on the host immune response in the context of bacterial or viral infections remains largely unknown. Here, we aimed to investigate the impact of voluntary wheel running (VWR), mimicking an active lifestyle, on the pulmonary immune system and to which extent a lack of exercise might affect the severity of pneumonia induced by bacterial L. longbeachae or viral influenza A virus (IAV) infection. We observed that VWR enhanced stamina to exercise and reduced visceral adipose tissue. Moreover, VWR induced the expression of myokines and lipolysis-associated genes and decreased the number of circulating monocytes. Notably, neither acute nor long-term (2 and 8 weeks, respectively) physical exercise significantly affected the abundance or metabolism of pulmonary immune cells in healthy mice. However, upon infection with L. longbeachae, acute physical training reduced pathogen burden, dampened anorexia-induced weight loss, and decreased the recruitment of neutrophils and monocytes to the airways. Additionally, pro-inflammatory cytokines associated with bacterial clearance, including IFN-γ & TNFα increased in the lungs of exercised mice. Notably, VWR enhanced the potential to produce TNFa in both alveolar macrophages and infiltrating monocytes early and late in infection with L. longbeachae. Furthermore, in running mice we found increased mitochondrial and glucose dependency in myeloid cells, crucial for the inhibition of pathogen replication. Our results also show that CD4+ T cells from trained animals display reduced IFN-γ production, suggesting that exercise may predominantly boost the innate immune response. In contrast, during IAV infection, we observed significantly decreased numbers of activated type 1 helper T (Th1) cells in running mice, critical for viral clearance. However, the frequency of tetramer CD4+ and CD8+ T cells was increased, indicating higher antigen specificity of the immune response. Additionally, we found higher viral RNA content in lung tissue from exercising mice, and elevated production of pro-inflammatory cytokines including type I interferons. Moreover, we found higher expression of interferon-signalling genes in the pulmonary tissue of exercising mice. VWR increased the gene expression of Ifng in CD44+ CD4+ T cells in running mice, suggesting an enhanced capacity of CD4+ T cells to produce IFN-γ. Notably, VWR increased the expression of tissue-residency markers on CD8+ T cells. Taken together, our results suggest that VWR might have opposing effects on pulmonary immunity during infection. Hence, we conclude that acute physical exercise might enhance protection against bacterial invasion (L. longbeachae) by specifically boosting the innate immune response. In contrast, VWR reduces Th1-mediated anti-viral responses and increases the pulmonary viral RNA content, suggesting that physical exercise might enhance the susceptibility to IAV infection. However, by boosting the adaptive IFN-γ-mediated anti-viral response, antigen-specificity, and increasing tissue residency, exercise may enhance the defence against secondary viral infections

Mechanism of Action Analyses of Cell Wall Synthesis Inhibitors and Lipophilic Derivatives with Enhanced Antibiotic Activity

(noch nicht zugänglich / not yet accessible

Design and Multistep Synthesis of Ligands for the GPR18 and GPR183: Related Orphan G Protein-Coupled Receptors with Immunoregulatory Functions

(noch nicht zugänglich / not yet accessible

Tissue cell-type composition changes during aging in mice

Aging is linked to progressive alterations in organ functionality and a heightened susceptibility to various diseases. These age-related functional deteriorations are likely, in part, due to microstructural changes within organs, even in the absence of pathological conditions. Examining cellular composition at the organ-level across tissues traditionally posed significant challenges due to the high workload associated with the application of unbiased cell counting methods across a range of histological samples. Here, we employed bulk RNA-sequencing, coupled with deconvolution based on celltype specific markers, to generate datasets and derive estimates regarding agingassociated changes in cell-type composition across multiple tissues (brain, heart, lung, skeletal muscle, kidney, testis) in male C57BL/6J mice, covering much of their lifespan (3, 5, 8, 14, 20 and 26 month). We show that with advanced age, immune cell types showed predominant changes among all tested tissues. Across organs, most immune cells increased with advancing age while parenchymal cells showed a decreasing trend during aging. In addition, we mined publicly available RNA-seq datasets in mice to identify experimental conditions that either counteract or phenocopy aging-associated changes in cellular tissue composition. These analyses revealed, for instance, that diabetes phenocopies aging associated changes in the mouse kidney, and calorie restriction counteract aging in mice muscle. Additional well-established cell counting methodologies were used to confirm findings obtained using our deconvolution approach

G-quadruplex formation in mouse macrophages changes the immune response to bacterial infection

G-quadruplexes (G4s) are stable secondary structures that form in guanine-rich regions of DNA and RNA. Guanines bind via Hoogsteen hydrogen bonding and form G tetrads that stack upon each other and become stabilized by a cation in the center. Nowadays it is proven that G4s form in vivo and influence a variety of biological processes, including transcription, translation, replication, and telomere maintenance. More than 700,000 sites in the human and mouse genomes have the potential to form a G4. Since G4s are enriched in oncogenic promoters, they are targeted in cancer therapy. The contribution of tumor-associated macrophages (TAMs) in the tumor environment has been controversially discussed. Therefore, linking cancer and inflammation and analyzing the role of G4s in macrophages is an emerging research question. The here presented doctoral thesis provides a detailed analysis of the role of G4s in mouse macrophages during bacterial infection mimicked by lipopolysaccharide (LPS). It was shown that G4s form in macrophages and can be stabilized by the G4-specific ligand pyridostatin (PDS). While the key macrophages function of phagocytosis was unaffected by G4 stabilization, G4 formation was shown to reduce the immune response-related cytokine expression and secretion. These transcriptome-wide changes affecting the immune response to bacteria are modulated by changes in the activity of the transcription factor NF-κB, a master regulator in orchestrating host defense. ATAC-Seq to map the chromatin landscape revealed that G4 stabilization modulates the accessibility of transcription start sites which could explain the transcriptomic changes. The data presented here provide the basis for a novel role of G4s in the immune response to bacteria in macrophages. These findings open the possibility to discuss G4s as a drug target to control the immune response, for example during an endotoxic shock (sepsis) induced by exposure to LPS

Mechanicalstress and Proteostasis : analysis of the effect of mechanical stress at various levels of cellular organization

(noch nicht zugänglich / not yet accessible