Regarding Distant Suffering : Audience engagement with representations of humanitarian disaster

Until very recently, academic debates on distant suffering have been informed largely either by empirical studies on representation or by theoretical reflections on the audience-sufferer relationship. Arguably, this scarcity of audience research in the field has allowed overly pessimistic accounts to long remain unchallenged. This dissertation aims to add to the small, albeit growing, body of studies that investigate empirically how audiences engage with representations of humanitarian disaster. The four empirical chapters explore audience engagement with distant suffering in three very different contexts: an interactive app, an online video campaign and a television news item. Results suggest that substantial parts of the audience are willing and able to be emotionally moved by depictions of humanitarian disaster, to express their engagement in various – often unpredictable – ways, and to even reflect on causes and moral significance of mediated distant suffering. While this dissertation also brings to the fore some of the fundamental limitations of engagement, the findings suggest that a position of excessive pessimism regarding audiences of distant suffering is not just unproductive but also unwarranted

The HLA ligandome of oropharyngeal squamous cell carcinomas reveals shared tumour-exclusive peptides for semi-personalised vaccination

Background The immune peptidome of OPSCC has not previously been studied. Cancer-antigen specific vaccination may improve clinical outcome and efficacy of immune checkpoint inhibitors such as PD1/PD-L1 antibodies. Methods Mapping of the OPSCC HLA ligandome was performed by mass spectrometry (MS) based analysis of naturally presented HLA ligands isolated from tumour tissue samples (n = 40) using immunoaffinity purification. The cohort included 22 HPV-positive (primarily HPV-16) and 18 HPV-negative samples. A benign reference dataset comprised of the HLA ligandomes of benign haematological and tissue datasets was used to identify tumour-associated antigens. Results MS analysis led to the identification of naturally HLA-presented peptides in OPSCC tumour tissue. In total, 22,769 peptides from 9485 source proteins were detected on HLA class I. For HLA class II, 15,203 peptides from 4634 source proteins were discovered. By comparative profiling against the benign HLA ligandomic datasets, 29 OPSCC-associated HLA class I ligands covering 11 different HLA allotypes and nine HLA class II ligands were selected to create a peptide warehouse. Conclusion Tumour-associated peptides are HLA-presented on the cell surfaces of OPSCCs. The established warehouse of OPSCC-associated peptides can be used for downstream immunogenicity testing and peptide-based immunotherapy in (semi)personalised strategies

Predicting DNA-Binding Specificities of Eukaryotic Transcription Factors

Today, annotated amino acid sequences of more and more transcription factors (TFs) are readily available. Quantitative information about their DNA-binding specificities, however, are hard to obtain. Position frequency matrices (PFMs), the most widely used models to represent binding specificities, are experimentally characterized only for a small fraction of all TFs. Even for some of the most intensively studied eukaryotic organisms (i.e., human, rat and mouse), roughly one-sixth of all proteins with annotated DNA-binding domain have been characterized experimentally. Here, we present a new method based on support vector regression for predicting quantitative DNA-binding specificities of TFs in different eukaryotic species. This approach estimates a quantitative measure for the PFM similarity of two proteins, based on various features derived from their protein sequences. The method is trained and tested on a dataset containing 1 239 TFs with known DNA-binding specificity, and used to predict specific DNA target motifs for 645 TFs with high accuracy

'They don’t deserve that' : moral responsibility in the face of mediated distant suffering

This paper explores audience reflections on issues of moral responsibility towards distant others in response to news images of the 2011 humanitarian crisis at the Horn of Africa. It has been argued that globalization processes carry the potential of broadening the scope of solidarity and care of people towards distant others (Chouliaraki, 2008; Linklater, 2007;Appadurai, 1996; Gerbner, 1969; Norris, 2000). In particular, it has been suggested that media representations that are embedded in a ‘cosmopolitan’ discourse can encourage an increasingly global moral horizon in audiences (Chouliaraki, 2006; Linklater, 2007; Beck and Cronin, 2006). It is this line of argumentation that is further explored in our study. Research on audiences of distant suffering has typically focused on emotional responses such as compassion or care (Höijer, 2004; Kyriakidou, 2008; Moeller, 1999) with only few exceptions exploring cognitive aspects such as denial (Seu, 2010; Cohen, 2001). Our study aims to add to the academic debate by placing the empirical focus on more cognitive aspects of spectatorship. Based on six focus groups (total of 27 participants), the study investigates audience reflections on moral responsibility in reaction to cosmopolitan representations of distant suffering. One of the starting points of our study – distinguishing it from much of the earlier work in the field – is the proposition that people can become morally engaged by moral reasoning despite (a lack of) emotional responses such as compassion, sympathy or empathy (e.g. Haidt, 2003). The study thereby also answers calls for more empirical efforts to explore spectatorship of distant suffering, voiced by various authors in the field (Joye, 2013; Seu, 2010; Ong, 2009; Höijer, 2004). Participants were asked to watch and subsequently discuss a 4-minute television news item on the Horn of Africa crisis broadcast by the NOS Journaal. The item included a human interest story of a Somali refugee family, first-hand accounts of a grieving father, as well as background information about the genesis of the crisis. Clearly an instance of what Chouliaraki (2012) would denote as ‘emergency news’, the item features many representational aspects of a cosmopolitan discourse. We found that after watching the video, discussions quickly gravitated towards possible actions to help. Participants typically expressed both responsibility and willingness to act and were most prepared to donate money to small-scale charity organisations. Yet, most also assigned significant responsibility to bigger (inter-)national (non-)governmental organisations though they did not see themselves play a part in these bigger social structures. Strikingly, discussions revealed that individual moral responsibility was felt mostly for short-term alleviation of suffering. Responsibility for long-term solutions was attributed to (inter-)national (non-)governmental organisations. By emphasizing such organisations, participants attenuated their own moral responsibilities and feelings of guilt. Surprisingly, representational practices constitutive of a cosmopolitan discourse (e.g. the human interest focus of the news item) did not emerge as pivotal for experiencing moral responsibility. Rather, it was more the participants’ privileged Western and Dutch backgrounds, living in a well-to-do society (opposed to poor, underdeveloped, undereducated African ('victims') that contributed to a sense of moral responsibility

Neurogenesis and widespread forebrain migration of distinct GABAergic neurons from the postnatal subventricular zone

Most forebrain GABAergic interneurons in rodents are born during embryonic development in the ganglionic eminences (GE) and migrate tangentially into the cortical plate. A subset, however, continues to be generated postnatally in the subventricular zone (SVZ). These interneurons populate the olfactory bulb (OB) reached via migration in the rostral migratory stream (RMS). Employing transgenic mice expressing EGFP in 5-HT3-positive neurons, we identified additional migratory pathways in the early postnatal brain. Time-lapse imaging experiments revealed massive migration of EGFP-positive cells from the SVZ into numerous forebrain regions, including cortex, striatum, and nucleus accumbens. The neuronal fate of the migratory EGFP-labeled cells was indicated by their doublecortin (DCX) expression. Birthdating experiments, by using 5-bromo-2′-deoxyuridine (BrdU) and retrovirus-based experiments, provided evidence that migrating neuroblasts were born in the SVZ postnatally and developed a distinct GABAergic phenotype. Our results demonstrate that the SVZ is a reservoir of GABAergic interneurons not only for the OB, but also for other cortical and subcortical areas

Age dependency of body mass index distribution in childhood and adolescent inpatients with anorexia nervosa with a focus on DSM-5 and ICD-11 weight criteria and severity specifiers

Both DSM-5 and ICD-11 have provided weight cut-offs and severity specifiers for the diagnosis of anorexia nervosa (AN) in childhood, adolescence and adulthood. The aims of the current study focusing on inpatients aged < 19 years were to assess (1) the relationship between age and body mass index (BMI; kg/m2), BMI-centiles, BMI-standard deviation scores (BMI-SDS) and body height-SDS at referral, (2) the percentages of patients fulfilling the DSM-5 and ICD-11 weight criteria and severity categories for AN, and (3) the validity of the AN severity specifiers via analysis of both weight related data at discharge and inpatient treatment duration. The German Registry for Anorexia Nervosa encompassed complete data sets for 469 female patients (mean age = 15.2 years; range 8.9-18.9 years) with a diagnosis of AN (n = 404) or atypical AN (n = 65), who were ascertained at 16 German child and adolescent psychiatric hospitals. BMI at referral increased up to age 15 to subsequently plateau. Approximately one tenth of all patients with AN had a BMI above the fifth centile. The ICD-11 specifier based on a BMI-centile of 0.3 for childhood and adolescent AN entailed two equally sized groups of patients. Discharge data revealed limited validity of the specifiers. Height-SDS was not correlated with age thus stunting had no impact on our data. We corroborate the evidence to use the tenth instead of the fifth BMI-centile as the weight criterion in children and adolescents. Weight criteria should not entail major diagnostic shifts during the transition from adolescence to adulthood. The severity specifiers based on BMI or BMI-centiles do not seem to have substantial clinical validity

Interleukin-4 receptor signaling modulates neuronal network activity

Evidence is emerging that immune responses not only play a part in the central nervous system (CNS) in diseases but may also be relevant for healthy conditions. We discovered a major role for the interleukin-4 (IL-4)/IL-4 receptor alpha (IL-4R alpha) signaling pathway in synaptic processes, as indicated by transcriptome analysis in IL-4R alpha-deficient mice and human neurons with/without IL-4 treatment. Moreover, IL-4R alpha is expressed presynaptically, and locally available IL-4 regulates synaptic transmission. We found reduced synaptic vesicle pools, altered postsynaptic currents, and a higher excitatory drive in cortical networks of IL-4R alpha-deficient neurons. Acute effects of IL-4 treatment on postsynaptic currents in wild-type neurons were mediated via PKC gamma signaling release and led to increased inhibitory activity supporting the findings in IL-4R alpha-deficient neurons. In fact, the deficiency of IL-4R alpha resulted in increased network activity in vivo, accompanied by altered exploration and anxiety-related learning behavior; general learning and memory was unchanged. In conclusion, neuronal IL-4R alpha and its presynaptic prevalence appear relevant for maintaining homeostasis of CNS synaptic function