The Heat Shock Protein 90 (HSP90) Is Required for the IL-33-Induced Cytokine Production in Mast Cells (MCs)

The alarmin interleukin-33 (IL-33) is released upon cell stress and damage in peripheral tissues. The receptor for IL-33 is the Toll/Interleukin-1 receptor (TIR)-family member T1/ST2 (the IL-33R), which is highly and constitutively expressed on MCs. The sensing of IL-33 by MCs induces the MyD88−TAK1−IKK2-dependent activation of p65/RelA and MAP-kinases, which mediate the production of pro-inflammatory cytokines and amplify FcεRI-mediated MC-effector functions and the resulting allergic reactions. Therefore, the investigation of IL-33-induced signaling is of interest for developing therapeutic interventions effective against allergic reactions. Importantly, beside the release of IL-33, heat shock proteins (HSPs) are upregulated during allergic reactions. This maintains the biological functions of signaling molecules and/or cytokines but unfortunately also strengthens the severity of inflammatory reactions. Here, we demonstrate that HSP90 does not support the IL-33-induced and MyD88−TAK1−IKK2-dependent activation of p65/RelA and of mitogen-activated protein (MAP)-kinases. We found that HSP90 acts downstream of these signaling pathways, mediates the stability of produced cytokine mRNAs, and therefore facilitates the resulting cytokine production. These data show that IL-33 enables MCs to perform an effective cytokine production by the upregulation of HSP90. Consequently, HSP90 might be an attractive therapeutic target for blocking IL-33-mediated inflammatory reactions

Geburtenplanung, soziale Ungleichheit und Geschlecht: das Beispiel Stuttgart während der Industrialisierung

'Das Modell der Demographischen Transition und die demographische Forschung zum Geburtenrückgang im späten 19. und während des 20. Jahrhunderts beschäftigen sich zwar mit grundlegenden menschlichen Verhaltensweisen, das Geschlecht der Akteure spielt in den Analysen jedoch bestenfalls eine untergeordnete Rolle. Zumeist wird Familienplanung nicht als Ergebnis bewusster Entscheidungen von Paaren, von Männern und Frauen diskutiert. Der Beitrag kombiniert ausgewählte demographische Ergebnisse mit Überlegungen zu Genderaspekten des Modells der Demographischen Transition. Als Grundlage dient ein Datensatzes mit ca. 5000 Rekonstitutionen von Stuttgarter Familien (1830-1910). Er beinhaltet Informationen zum Heiratsverhalten, zu Gebürtigkeit und Sterblichkeit, aber auch zur beruflichen und sozialen Lage. Die Analyse der Stuttgarter Daten belegt die Vorreiterrolle der frühbürgerlichen gebildeten Angestellten- und Beamtenschaft, des Kerns des sich im Laufe des 19. Jahrhunderts ausformenden Bildungsbürgertums. Die Kombination des (männlichen) Berufs mit der geschlechtsspezifischen Aufgabenteilung in Erwerbsarbeit und Haushaltsorganisation, die diese soziale Gruppierung charakterisieren, lenkt den Blick auf den kulturellen Hintergrund individueller geburtenplanerischer Beweggründe und auf die demographischen Folgen der Durchsetzung des bürgerlichen Geschlechtermodells. Deutlich sichtbar wird auch die Rolle von Frauen bei innerfamiliären Entscheidungen in geburtenplanerischer Absicht.' (Autorenreferat)'The model of demographic transition and the research about fertility decline deals with elementary human behaviour but it seems to be 'without gender'. In general, family-planning is not treated as a question of conscious decisions of couples, women and men. Constructing a model of the demographic transition which takes into account gender, it is necessary to combine this model with findings from social history, gender history and cultural history with regard to the processes of the rise of a bourgeois middle class with special forms of organization work and family. This paper puts up some demographic results for discussion combined with questions of gender and demographic transition mentioned above. As source the authors can use a demographic database on 5,000 nineteenth-century families out of Stuttgart (1830-1910) containing data on marriage behaviour, births, and mortality, as well as numerous other data. The results demonstrate the importance and pioneering role of the early modern educated civil servants - the core of what was to become the modern educated middle class. Combining profession and the gender-specific division of work and family's household in this social group, they can show cultural patterns of motivation to reduce births and the demographic results of the inforcement of the bourgeois gender model. Above all, the authors can show the importance of women in decision making about birth control.' (author's abstract

State-level trends in sudden unexpected infant death and immunization in the United States: an ecological study

Background: Sudden unexpected infant death (SUID) continues to be a major contributor to infant mortality in the United States. The objective was to analyze time trends in SUID and their association with immunization coverage. Methods: The number of deaths and live births per year and per state (1992-2015) was obtained from the Centers for Disease Control and Prevention (CDC). We calculated infant mortality rates (i.e., deaths below one year of age) per 1000 live births for SUID. We obtained data on immunization in children aged 19-35 months with three doses or more of diphtheria-tetanus-pertussis (3+ DTP), polio (3+ Polio), and Haemophilus influenzae type b (3+ Hib) as well as four doses or more of DTP (4+ DTP) from the National Immunization Survey, and data on infant sleep position from the Pregnancy Risk Assessment Monitoring System (PRAMS) Study. Data on poverty and race were derived from the Current Population and American Community Surveys of the U.S. Census Bureau. We calculated mean SUID mortality rates with 95% confidence interval (CI) as well as the annual percentage change using breakpoint analysis. We used Poisson regression with random effects to examine the dependence of SUID rates on immunization coverage, adjusting for sleep position and poverty (1996-2015). In a second model, we additionally adjusted for race (2000-2015). Results: Overall, SUID mortality decreased in the United States. The mean annual percent change was - 9.6 (95% CI = - 10.5, - 8.6) between 1992 and 1996, and - 0.3 (95% CI = - 0.4, - 0.1) from 1996 onwards. The adjusted rate ratios for SUID mortality were 0.91 (95% CI = 0.80, 1.03) per 10% increase for 3+ DTP, 0.88 (95% CI = 0.83, 0.95) for 4+ DTP, 1.00 (95% CI = 0.90, 1.10) for 3+ polio, and 0.95 (95% CI = 0.89, 1.02) for 3+ Hib. After additionally adjusting for race, the rate ratios were 0.76 (95% CI = 0.67, 0.85) for 3+ DTP, 0.83 (95% CI = 0.78, 0.89) for 4+ DTP, 0.81 (95% CI = 0.73, 0.90) for 3+ polio, and 0.94 (95% CI = 0.88, 1.00) for 3+ Hib. Conclusions: SUID mortality is decreasing, and inversely related to immunization coverage. However, since 1996, the decline has slowed down

Ischemia/Reperfusion Injury in Liver Surgery and Transplantation: Pathophysiology

Liver ischemia/reperfusion (IR) injury is caused by a heavily toothed network of interactions of cells of the immune system, cytokine production, and reduced microcirculatory blood flow in the liver. These complex networks are further elaborated by multiple intracellular pathways activated by cytokines, chemokines, and danger-associated molecular patterns. Furthermore, intracellular ionic disturbances and especially mitochondrial disorders play an important role leading to apoptosis and necrosis of hepatocytes in IR injury. Overall, enhanced production of reactive oxygen species, found very early in IR injury, plays an important role in liver tissue damage at several points within these complex networks. Many contributors to IR injury are only incompletely understood so far. This paper tempts to give an overview of the different mechanisms involved in the formation of IR injury. Only by further elucidation of these complex mechanisms IR injury can be understood and possible therapeutic strategies can be improved or be developed

Host-specific symbiotic requirement of BdeAB, a RegR-controlled RND-type efflux system in Bradyrhizobium japonicum

Multidrug efflux systems not only cause resistance against antibiotics and toxic compounds but also mediate successful host colonization by certain plant-associated bacteria. The genome of the nitrogen-fixing soybean symbiont Bradyrhizobium japonicum encodes 24 members of the family of resistance/nodulation/cell division (RND) multidrug efflux systems, of which BdeAB is genetically controlled by the RegSR two-component regulatory system. Phylogenetic analysis of the membrane components of these 24 RND-type transporters revealed that BdeB is more closely related to functionally characterized orthologs in other bacteria, including those associated with plants, than to any of the other 23 paralogs in B. japonicum. A mutant with a deletion of the bdeAB genes was more susceptible to inhibition by the aminoglycosides kanamycin and gentamicin than the wild type, and had a strongly decreased symbiotic nitrogen-fixation activity on soybean, but not on the alternative host plants mungbean and cowpea, and only very marginally on siratro. The host-specific role of a multidrug efflux pump is a novel feature in the rhizobia-legume symbioses. Consistent with the RegSR dependency of bdeAB, a B. japonicum regR mutant was found to have a greater sensitivity against the two tested antibiotics and a symbiotic defect that is most pronounced for soybea

International time trends in sudden unexpected infant death, 1969–2012

Background: Sudden unexpected infant death (SUID) - including sudden infant death syndrome (SIDS) - continues to be a major contributor to infant mortality worldwide. Our objective was to analyse time trends and to identify country-clusters. Methods: The National Statistical Offices of 52 countries provided the number of deaths and live births (1969-2012). We calculated infant mortality rates per 1000 live births for SUID, SIDS, and all-cause mortality. Overall, 29 countries provided sufficient data for time course analyses of SUID. To sensitively model change over time, we smoothed the curves of mortality rates (1980-2010). We performed a hierarchical cluster analysis to identify clusters of time trends for SUID and SIDS, including all-cause infant mortality. Results: All-cause infant mortality declined from 28.5 to 4.8 per 1000 live births (mean 12.4; 95% confidence interval 12.0-12.9) between 1969 and 2012. The cluster analysis revealed four country-clusters. Clusters 1 and 2 mostly contained countries showing the typical peak of SUID mortality during the 1980s. Cluster 1 had higher SUID mortality compared to cluster 2. All-cause infant mortality was low in both clusters but higher in cluster 1 compared to cluster 2. Clusters 3 and 4 had low rates of SUID without a peak during the 1980s. Cluster 3 had the highest all-cause infant mortality of all clusters. Cluster 4 had an intermediate all-cause infant mortality. The time trends of SUID and SIDS mortality were similar. Conclusions: The country-specific time trends in SUID varied considerably. The identification of country-clusters may promote research into how changes in sleep position, smoking, immunisation, or other factors are related to our findings

Childhood abuse and adult sociocognitive skills : distinguishing between self and other following early trauma

Experience of childhood abuse (CA) impairs complex social functioning in children; however, much less is known about its effects on basic sociocognitive processes and even fewer studies have investigated these in adult survivors. Using two behavioral tasks, this study investigated spontaneous theory of mind (ToM) and imitative behavior in 41 women with CA and 26 unaffected comparison (UC) women. In the spontaneous ToM task, UCs showed a larger ToM index than CAs, indicating more facilitation by knowledge of another's false belief. In the imitation-inhibition task, CAs experienced less interference than UCs when observing another's incongruent movements. After controlling for depression, differences in ToM became marginally significant, yet remained highly significant for inhibiting imitative behavior. The findings suggest CA survivors have altered perspective-taking and are less influenced by others' perspectives, potentially due to changes in self-other distinction. Clinical implications regarding therapeutic practice with survivors of CA are discussed

Elevated Atmospheric {CO}2 Modifies Mostly the Metabolic Active Rhizosphere Soil Microbiome in the Giessen {FACE} Experiment

Elevated levels of atmospheric CO2 lead to the increase of plant photosynthetic rates, carbon inputs into soil and root exudation. In this work, the effects of rising atmospheric CO2 levels on the metabolic active soil microbiome have been investigated at the Giessen free-air CO2 enrichment (Gi-FACE) experiment on a permanent grassland site near Giessen, Germany. The aim was to assess the effects of increased C supply into the soil, due to elevated CO2, on the active soil microbiome composition. RNA extraction and 16S rRNA (cDNA) metabarcoding sequencing were performed from bulk and rhizosphere soils, and the obtained data were processed for a compositional data analysis calculating diversity indices and differential abundance analyses. The structure of the metabolic active microbiome in the rhizospheric soil showed a clear separation between elevated and ambient CO2 (p = 0.002); increased atmospheric CO2 concentration exerted a significant influence on the microbiomes differentiation (p = 0.01). In contrast, elevated CO2 had no major influence on the structure of the bulk soil microbiome (p = 0.097). Differential abundance results demonstrated that 42 bacterial genera were stimulated under elevated CO2. The RNA-based metabarcoding approach used in this research showed that the ongoing atmospheric CO2 increase of climate change will significantly shift the microbiome structure in the rhizosphere