Legionella pneumophila strain 130b evades macrophage cell death independent of the effector SidF in the absence of flagellin

International audienceThe human pathogen Legionella pneumophila must evade host cell death signaling to enable replication in lung macrophages and to cause disease. After bacterial growth, however, L. pneumophila is thought to induce apoptosis during egress from macrophages. The bacterial effector protein, SidF, has been shown to control host cell survival and death by inhibiting pro-apoptotic BNIP3 and BCL-RAMBO signaling. Using live-cell imaging to follow the L. pneumophila-macrophage interaction, we now demonstrate that L. pneumophila evades host cell apoptosis independent of SidF. In the absence of SidF, L. pneumophila was able to replicate, cause loss of mitochondria membrane potential, kill macrophages, and establish infections in lungs of mice. Consistent with this, deletion of BNIP3 and BCL-RAMBO did not affect intracellular L. pneumophila replication, macrophage death rates, and in vivo bacterial virulence. Abrogating mitochondrial cell death by genetic deletion of the effectors of intrinsic apoptosis, BAX, and BAK, or the regulator of mitochondrial permeability transition pore formation, cyclophilin-D, did not affect bacterial growth or the initial killing of macrophages. Loss of BAX and BAK only marginally limited the ability of L. pneumophila to efficiently kill all macrophages over extended periods. L. pneumophila induced killing of macrophages was delayed in the absence of capsase-11 mediated pyroptosis. Together, our data demonstrate that L. pneumophila evades host cell death responses independently of SidF during replication and can induce pyroptosis to kill macrophages in a timely manner

Advertising Unhealthy Food to Children: on the Importance of Regulations, Parenting Styles, and Media Literacy

<jats:title>Abstract</jats:title><jats:sec><jats:title>Purpose of Review</jats:title><jats:p>Childhood obesity is a global health concern. And a number of studies have indicated that food promotions affect children’s food attitudes, preferences, and food choices for foods high in fat and sugar, which potentially impacts children’s body weight development. This review showcases how children are affected by food promotions, why companies even target children with their promotional efforts, and what makes children so susceptible to promotion of unhealthy food. In addition, this review discusses how regulations, parental styles, and individual media literacy skills can help to contain the potential detrimental effects of food promotions on children’s health.</jats:p></jats:sec><jats:sec><jats:title>Recent Findings</jats:title><jats:p>The recent findings indicate that children are affected by food promotions in their preference for unhealthy food and beverages in selection tasks shortly conducted after exposure. Furthermore, results indicate significant effects of food marketing, including enhanced attitudes, preferences, and increased consumption of marketed (predominantly unhealthy) foods connected with a wide range of marketing strategies. Children are particularly vulnerable to promotional efforts and react to it strongly due to their still developing cognitive and social skills as well as their lack in inhibitory control.</jats:p></jats:sec><jats:sec><jats:title>Summary</jats:title><jats:p>This review proposes an applied focus that discusses pathways for regulators, parents, and educators. In the light of the discussed results, a large number of studies on food promotion indicate that there is need to react. In all these measures, however, it is of relevance to consider children’s developmental stages to effectively counteract and respond to the potential detrimental effects of food promotions on children’s long-term weight development.</jats:p></jats:sec&gt

Selling stories of social justice. How consumers react to and learn from social ads

Advertising strategies are constantly changing and today, companies often take a position regarding current social topics in their advertis-ing messages. With two experimental studies using actual ads, we explore how people react to and learn from social ads regarding particular social issues they tackle. With the first study, we examine whether an ad that deals with modern sexism raises awareness about this issue and whether it performs more effectively than a non-narra-tive, informative video (TED-talk) with the same topic. Second, as corporate social responsibility (CSR) ads are discussed to be received controversial among viewers, we explore how a social ad communi-cating a CSR message (gay rights) compared to a “classic” product ad performs on brand-relevant outcomes. Both studies indicate that raising awareness for a social issue through social ads could poten-tially backfire and might only work under certain circumstances. Advertisers, therefore, should elaborate on how they integrate CSR ads into their marketing strategies

Metabolomics to unveil and understand phenotypic diversity between pathogen populations

Visceral leishmaniasis is caused by a parasite called Leishmania donovani, which every year infects about half a million people and claims several thousand lives. Existing treatments are now becoming less effective due to the emergence of drug resistance. Improving our understanding of the mechanisms used by the parasite to adapt to drugs and achieve resistance is crucial for developing future treatment strategies. Unfortunately, the biological mechanism whereby Leishmania acquires drug resistance is poorly understood. Recent years have brought new technologies with the potential to increase greatly our understanding of drug resistance mechanisms. The latest mass spectrometry techniques allow the metabolome of parasites to be studied rapidly and in great detail. We have applied this approach to determine the metabolome of drug-sensitive and drug-resistant parasites isolated from patients with leishmaniasis. The data show that there are wholesale differences between the isolates and that the membrane composition has been drastically modified in drug-resistant parasites compared with drug-sensitive parasites. Our findings demonstrate that untargeted metabolomics has great potential to identify major metabolic differences between closely related parasite strains and thus should find many applications in distinguishing parasite phenotypes of clinical relevance

Shaping Healthy Eating Habits in Children With Persuasive Strategies: Toward a Typology

There is an abundance of evidence that the presentation of unhealthy foods (UHFs) in different media has the power to shape eating habits in children. Compared to this rich body of work with regard to the effects of UHF presentations, studies testing the effects of healthy foods (HFs) are less conclusive. In particular, while the persuasive mechanisms behind HF presentations are well-understood, we lack insights about the role of messages factors, that is, how are (and should) HFs (be) presented in order to foster healthy eating habits in children. This paper tackles this research gap by suggesting the Persuasive Strategies Presenting Healthy Foods to Children (PSPHF) typology, classified along three pillars: (a) composition-related characteristics, (b) source-related characteristics, and (c) information-related characteristics. Against the background of the PSPHF typology, we review the available empirical evidence, outline pressing research gaps, and discuss implications for researchers, health promoters, and program planers

Social Web-Nutzung und politische Partizipation österreichischer Jugendlicher

Politische Partizipation ist ein bedeutender Bestandteil von funktionierenden Demokratien. Es zeichnet sich jedoch in westlichen Staaten ein immer stärkerer Rückgang von politischer Beteiligung ab. Nicht nur die Wahlbeteiligung sinkt, auch andere Formen, wie die Teilnahme an Demonstrationen und politischen Veranstaltungen oder die Unterstützung von direkten Demokratieformen wie Volksbegehren, verlieren immer stärker an Bedeutung. Das Internet hat hier die Hoffnung geschürt neue, attraktive Formen der politischen Partizipation zu eröffnen und diese insbesondere bei der traditionell als passiv eingestuften Bevölkerungsgruppe, den Jugendlichen, zu verbreiten. Da diese als die HauptuserInnen des Social Webs angesehen werden, sind sie die großen HoffnungsträgerInnen der neuen Beteiligungsformen. Aktuelle Ereignisse wie der Arabische Frühling oder die breite Thematisierung der Online-Aktion des Vereins „Invisible Children“ und ihrer Ziele im Bezug auf den ugandischen Rebellenführer Joseph Kony geben diesen Hoffnungen neuen Nährboden. Auf Basis einer repräsentativen Studie aus dem Jahr 2010 über Mediennutzung, politische Partizipation und politischer Interesse österreichischer Befragter (N= 2.954), wird das Potenzial des Social Webs im Bezug auf politische Beteiligung ausgewertet. Im Mittelpunkt dieser Arbeit steht der Einfluss der Medienkompetenz und des Bildungsgrads auf den Level der politischen Online-Beteiligung. Die Ergebnisse zeigen, dass unabhängig vom Grad der Bildung Menschen das Netz für Online-Beteiligung nutzen. Besonders für Jugendliche zeigt sich politische Online-Partizipation als attraktives Instrument. Offen bleibt jedoch, wie das politische Interesse vergrößern werden kann. Denn trotzdem sich andere Bevölkerungsruppen als die traditionell politisch Engagierten im Internet beteiligen, lässt sich ein großes Maß der politischen Online-Partizipation auf die Beteiligung in der Offline-Welt zurückführen.Political participation is an important part of a functioning democracy. In western states there is a significant decline of participation. This gets apparent in the low voter turnout and the regressing of direct democracy as the contribution on referendums. As the internet got more popular, hope was rising that new forms of participation could eventually develop. Adolescents, who are usually not in the group of political activists, are the main users of the social web. This is why the hope of a political change is primarily built on them. The “Arabic Spring” and other recent events like the involvement of many social web users in the online-activities of the organization “Invisible Children” and their political goals, regarding the capture of Ugandan rebel leader Joseph Kony, lead to a new discussion of the political potential of the social web. This analysis is based on a representative survey from 2010 on the use of media and political activities of Austrian respondents (N= 2.954). Object of study is the effect of social web use for political purposes on the political participation in real life of adolescents. The main focus is on the influence of the acquired media-competence and the education level on political participation online. The results show that education is not an important indicator for political participation online. Especially adolescents use the social web for political participation. There is no answer to the question how more people, who are politically interested, can be found. Although people who are usually not engaged in political debates do participate online, most of the people who participate on the internet show their political interest and participation offline as well

Conserved motifs reveal details of ancestry and structure in the small tim chaperones of the mitochondrial intermembrane space

The mitochondrial inner and outer membranes are composed of a variety of integral membrane proteins, assembled into the membranes posttranslationally. The small translocase of the inner mitochondrial membranes (TIMs) are a group of ∼10 kDa proteins that function as chaperones to ferry the imported proteins across the mitochondrial intermembrane space to the outer and inner membranes. In yeast, there are 5 small TIM proteins: Tim8, Tim9, Tim10, Tim12, and Tim13, with equivalent proteins reported in humans. Using hidden Markov models, we find that many eukaryotes have proteins equivalent to the Tim8 and Tim13 and the Tim9 and Tim10 subunits. Some eukaryotes provide "snapshots" of evolution, with a single protein showing the features of both Tim8 and Tim13, suggesting that a single progenitor gene has given rise to each of the small TIMs through duplication and modification. We show that no "Tim12" family of proteins exist, but rather that variant forms of the cognate small TIMs have been recently duplicated and modified to provide new functions: the yeast Tim12 is a modified form of Tim10, whereas in humans and some protists variant forms of Tim9, Tim8, and Tim13 are found instead. Sequence motif analysis reveals acidic residues conserved in the Tim10 substrate-binding tentacles, whereas more hydrophobic residues are found in the equivalent substrate-binding region of Tim13. The substrate-binding region of Tim10 and Tim13 represent structurally independent domains: when the acidic domain from Tim10 is attached to Tim13, the Tim8–Tim13¹⁰ complex becomes essential and the Tim9–Tim10 complex becomes dispensable. The conserved features in the Tim10 and Tim13 subunits provide distinct binding surfaces to accommodate the broad range of substrate proteins delivered to the mitochondrial inner and outer membranes

Therapeutic Efficacy of Stable Analogues of Vasoactive Intestinal Peptide against Pathogens

Vasoactive intestinal peptide (VIP) is an anti-inflammatory neuropeptide recently identified as a potential antimicrobial peptide. To overcome the metabolic limitations of VIP, we modified the native peptide sequence and generated two stable synthetic analogues (VIP51 and VIP51(6–30)) with better antimicrobial profiles. Herein we investigate the effects of both VIP analogues on cell viability, membrane integrity, and ultrastructure of various bacterial strains and Leishmania species. We found that the two VIP derivatives kill various non-pathogenic and pathogenic Gram-positive and Gram-negative bacteria as well as the parasite Leishmania major through a mechanism that depends on the interaction with certain components of the microbial surface, the formation of pores, and the disruption of the surface membrane. The cytotoxicity of the VIP derivatives is specific for pathogens, because they do not affect the viability of mammalian cells. Docking simulations indicate that the chemical changes made in the analogues are critical to increase their antimicrobial activities. Consequently, we found that the native VIP is less potent as an antibacterial and fails as a leishmanicidal. Noteworthy from a therapeutic point of view is that treatment with both derivatives increases the survival and reduces bacterial load and inflammation in mice with polymicrobial sepsis. Moreover, treatment with VIP51(6–30) is very effective at reducing lesion size and parasite burden in a model of cutaneous leishmaniasis. These results indicate that the VIP analogues emerge as attractive alternatives for treating drug-resistant infectious diseases and provide key insights into a rational design of novel agents against these pathogens.This work was supported, in whole or in part, by National Institutes of Health Grant RO1 AI031078 (to S. M. B.). This work was also supported by Excellence Grants from Junta de Andalucia (P09/CTS-4705) (to E. G.-R.) and European Cost Action (BM0802) (to E. G.-R.).Peer reviewe