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Doctors learn different communication approaches for use during prevention consultations to promote healthy habits, so as to set up a partnership and to promote patient autonomy. Three of these approaches are shared decision making, when there is more than one reasonable choice, motivational interviewing, principally for behaviour change and therapeutic education, a pedagogical approach helping patients develop skills so that they may have a better management of their chronic illness. This article presents an overview of the commonalities and the differences between these approaches, often considered separately, nevertheless they are complementary and in practice, using elements of all three during a consultation could improve preventative care.

During the pandemic, the world's media have publicized preliminary findings suggesting that tobacco use is protective against COVID-19. An ad hoc multidisciplinary group was created to address the major public health implications of this messaging. Key messages of this commentary are as follows: 1) The COVID-19 crisis may increase tobacco consumption and decrease access to healthcare. As a result, smoking-related morbidity and mortality could increase in the coming months and years; 2) Smoking and tobacco-related diseases are prognostic factors for severe COVID-19; and 3) In theory, smokers may be at lower risk of COVID-19 infection because of having fewer social contacts. In conclusion, tobacco control is a greater challenge than ever in the context of the COVID-19 pandemic. Public decision-makers must be vigilant in ensuring that public health practices are consistent and compliant with the principles of the WHO Framework Convention on Tobacco Control. In addition, researchers and the media have a responsibility to be cautious in communicating preliminary results that may promote non-evidence-based research, self-destructive individual behaviours, and commercial agendas.

Active-site directed probes are powerful in studies of enzymatic function. We report an active-site directed probe based on a warhead so far considered unreactive. By replacing the C-terminal carboxylate of ubiquitin (Ub) with an alkyne functionality, a selective reaction with the active-site cysteine residue of de-ubiquitinating enzymes was observed. The resulting product was shown to be a quaternary vinyl thioether, as determined by X-ray crystallography. Proteomic analysis of proteins bound to an immobilized Ub alkyne probe confirmed the selectivity toward de-ubiquitinating enzymes. The observed reactivity is not just restricted to propargylated Ub, as highlighted by the selective reaction between caspase-1 (interleukin converting enzyme) and a propargylated peptide derived from IL-1β, a caspase-1 substrate.

A brief definition of the consultation process is presented. Four different consultation programs (to schools, to a public health unit, to agencies for the handicapped and to a welfare agency) are described and the value of this process in providing service is stressed. Some indication of how the consultation process can be taught is mentioned and the need for more research and evaluation is emphasized.

In this thesis I explored the ins and outs of the multivesicular body, the pathways that intersect at this central endocytic compartment, the dynamics governing its lumen and how such processes impact various fields of cell biology and disease.

The two branches of our highly advanced immune system work closely together to detect and eliminate pathological threats. The first line of defense is provided by the innate immune system via detection of pathogenic or tumor cell fragments. Adaptive immune cells, on the other hand, recognize pathogens or malignant cells more specifically by scanning peptides, small protein fragments, presented by MHC molecules on other cells in our body. Specialized white blood cells (cytotoxic or killer T cells) can distinguish self- from non-self-peptides and directly eliminate cells that display signs of infection or mutation.The work described in this dissertation highlights how adaptive immunity can be used to our advantage, either from a therapeutic or diagnostic perspective. Immunotherapies that induce or promote anti-tumor or anti-viral responses have proven efficacious against infection and cancer. One strategy described is the development of chemically-modified epitopes as peptide vaccines, but small-molecule chemical drugs are also playing an increasing role in the field of cancer immunotherapy.In addition, monitoring of immune status and response to treatment, as well as mapping of epitopes, can aid diagnosis and design of treatment plans. The second part describes a novel method and application to visualize and monitor cytotoxic T cells.

Endocytosis is a crucial mechanism for the cell to maintain homeostasis. By vesicular transport the cell is able to take up cargo from the cell surface, send molecules to the plasma membrane for excretion or to regulate positioning of internalized cargo in the cell. This thesis describes the regulation of transport complexes associated to these vesicles that determines their movement in the cell. Through recruitment of RAB7GAP the GTPase Rab7 can be removed from the vesicular membrane, allowing for transport mediated by another GTPase called Arl8b.The second part of this thesis focusses on the bacterium Salmonella which manipulates the endosomal system in order to create a niche that supports its own survival. By excretion of effector molecules Salmonella imodulates the membrane content of vesicles and thereby prevents its own lysosomal degradation. This allows Salmonella to create a Salmonella containing vesicle compartment that benefits its own survival in the host cell. This thesis describes how release of these effector molecules can support transformation of host cells. These results explain the strrong correlation between gallbladder cancer and chronic S. Typhi infections observed in patients from countries like India, where S. Typhi infections are still common.

Malignant pleural mesothelioma (MPM) is an aggressive tumor of the mesothelial cells lining the pleura. The poor prognosis of patients indicates the importance to find more effective treatments. Therefore, this thesis focused on finding new treatment strategies for MPM. We present a method in which primary MPM cultures were chemically profiled to determine second-line treatment for patients. With this personalized treatment strategy we were able to predict individual patient responses to selected drugs. Based on the chemical profiles of all tumor cultures, these cultures could be divided in three groups. Transcriptomic analysis of these groups identified a unique genetic profile separating these groups and identifying the fibroblast growth factor receptor (FGFR) as a new target for the treatment of MPM. The cultures sensitive to FGFR inhibitors were dependent on FGFR3 mediated signaling which was regulated by BAP1, indicating BAP1 can serve as a biomarker for this treatment. Another target explored in this thesis was 5T4. We showed that 5T4 was only expressed in the tumor cells and that antibody-drug conjugates effectively kill high 5T4 expressing MPM cells. Altogether we present different promising novel strategies in the treatment of MPM, which could improve the survival outcome of these patients.

In this thesis the combinatorial use of bioorthogonal labelling and Electron Microscopy (EM)-based imaging techniques is explored to enable observations of specific molecular targets in their ultrastructural context within the cell.

The aim of this thesis is to explore the use of Bioorthogonal Antigens to study the cross-presentation pathway. Bioorthogonal Antigens are antigens carrying bioorthogonal groups in specific amino acid positions within the epitope region that can be reacted selectively within/on the cell using bioorthogonal ligation strategies. Incorporation of bioorthogonal groups into antigens has an advantage over other methods because most of the groups are stable to proteolysis and are small enough to have a minimal impact on routing and loading onto MHC-I molecules. In the future, these antigens have potential to be applied for imaging of the entire cross-presentation pathway using a single bioorthogonal handle.

Kinases play a role in many diseases including cancer, diabetes and infection diseases. Therefore, kinases are interesting drug targets. Inhibitors for some kinases are already in use as clinical drugs, however due to resistance and side effects, but also to target kinases related to diseases for which there is currently no treatment, research on the discovery of new classes of kinase inhibitors is imperative. To achieve this, not only new inhibitor classes need to be designed and synthesized, but also tools to profile kinases in physiological context and to determine the selectivity of inhibitors are required. The research in this thesis has focused on the development of more potent AKT1 and FLT3 kinase inhibitors and on the synthesis and application of new chemical tools for the profiling of kinases involved in various types of cancers and other diseases.In this thesis, new powerful tools and assays have been developed that unite the fields of synthetic chemistry, protein biochemistry and cell biology for the global analysis of kinase expression and function. The value of chemical profiling as a method for functional proteome analysis has been further highlighted by its application as a screen to evaluate the potency and selectivity of kinase inhibitors.

The paper deals with biographical, ideological and artistic links between Julian Tuwim, Alfred Döblin and Kurt Tucholsky. On the one hand, the basis of comparison are biographical similarities, the Jewish origin of those three writers, their family dramas, the experience of politically opressive school, the trauma of revolution or war, and the exile to name just a few. On the other hand, the article demonstrates the ways the modernity has influenced the attitudes and texts of Döblin, Tucholsky and Tuwim. While talking about modernity, the author focuses on such phenomena as secularisation and urbanisation processes, mass political movements, and new cultural challenges. Tuwim, Döblin and Tucholsky were born into assimilated Jewish families. Their perspective on the stereotypical Jews (the orthodox Jews as well as Jewish bankers or manufacturers) is marked with antipathy, or even contempt. The writers’ ambivalence towards the diapora and towards their own origin illustrate “Jewish self-hatred“; however, all three authors change their opinion on Jewry in the face of the growing anti-Semitic and Nazi danger, and especially the Holocaust. Döblin is proud of being Jewish after his visit to Poland in 1924, Tucholsky warns German Jews against the consequences of their passivitivy, and Tuwim publishes in 1944 his agitating manifesto We, Polish Jews. Last but not least, the three authors go into exile because of their Jewish ancestry and sociocultural activities. Therefore, it is no coincidence thatone cannot help having associations with Heinrich Heine: his biography can be interpreted as a prefiguration of a Jewish artist’s biography. Furthermore, Tuwim, Döblin and Tucholsky are notably sensitive to social questions, and their sensitivity to such issues results to some extent from their difficult childhood and youth. Especially significant seem in that respect family conflicts and the moving from city to city, since such experiences increase the feeling of loneliness and the vulnerability to depression. Nevertheless, Döblin, Tucholsky and Tuwim come with impetus into the cultural life of Germany and Poland and work in the areas of literature, cabaret (satire) as well as journalism. They share sympathy for the political left and fears of the orthodox communism. They are simultaneously advocates and ardent critics of great cities. They pay attention to new phenomena (the popularity of cars, the role of the press, the new morality) and react to them. Their aim is creating a culture which appeals to the masses and educates them in a non-intrusive way. However, the awareness of their own intellectual superiority imposes distance towards lower social groups. The distance stems, firstly, from the universal ambivalence artists feel towards the masses, and secondly, from the ideological moderation characteristic of petit bourgoisie and of the political centre. In general, Döblin, Tucholsky and Tuwim are idealists who hope for a humanitarian world which is impossible in the era of extrem political violence leading to the Holocaust.