Influence of inflammatory mechanisms in obese adipose tissue on pathomechanisms of allergic airway inflammation in mice

Asthma and obesity are non-communicable diseases with high and increasing prevalences. Both are characterized by the presence of local and systemic inflammatory processes, whereby their mutual pathomechanistic relationship within obesity-associated asthma are not fully elucidated. This research work hypothesized that inflammatory mechanisms in obese adipose tissue modify the inflammatory phenotype of an induced allergic airway inflammation (AAI) and that altered activation processes in CD4+ T cells are crucially involved. To test this hypothesis, BALB/c and C57BL/6 mice were fed for several weeks with a high-fat diet (HFD) in order to induce obesity-like metabolic changes and a mixed inflammatory phenotype of AAI was induced in the animals by exposure to house dust mite (HDM) extracts. In both strains, HFD resulted in comparable metabolic changes, such as higher plasma levels of a variety of metabolic parameters and features of type 2 diabetes. However, strain-dependent differences were observed with regard to excessive weight gain, which occurred only in C57BL/6 mice, but not in BALB/c mice. Weight gain in HFD-fed C57BL/6 mice was associated with pronounced adipocyte hypertrophy and increased inflammatory processes in the obese adipose tissue. As intended, HDM-exposure of control diet (ND)-fed mice resulted in a mixed inflammatory phenotype characterized by an influx of eosinophils and neutrophils in the bronchoalveolar lavage (BAL) and in lung tissue in both mouse strains. While per se no differences in the induced AAI between the HFD/HDM group and the ND/HDM group were detected in BALB/c mice, a more eosinophilic inflammation was observed in HFD-fed HDM-exposed C57BL/6 mice in comparison to their lean counterparts. Further investigations revealed increased levels of inflammatory cytokines in the BAL and higher numbers of inflammatory immune cells in the lung tissue of HFD/HDM C57BL/6 mice. This suggested that weight gain and associated inflammatory processes in obese adipose tissue are crucial for modifying characteristic features of the induced AAI. Single cell analysis of CD45+ lung cells was conducted to further analyze the cellular and molecular changes of the induced inflammatory phenotype in the airways of C57BL/6 mice. Interestingly, a CD4+ T cell subcluster was identified to be exclusively present in the lungs of lean, but not in obese HDM-exposed mice. In this subcluster, expression of markers associated with typical characteristics of Th2, Th1, and Treg cells and in addition, co-inhibitory receptors such as PD-1, CTLA-4, and LAG-3 was detected. Subsequent flow cytometric analyses confirmed the presence of Th2 and Treg cells expressing the coinhibitory receptors identified in lungs of HDM-exposed mice. To further investigate whether hypertrophic activated adipocytes release factors that might be involved in the regulation of co-inhibitory receptor expression of CD4+ T cells, supernatants from in vitro cultured adipocytes of HFD-fed mice were applied to differentiated Th2 and Treg cells. In line with the previous results, during the activation process lower numbers of Th2 cells were observed expressing CTLA-4 or LAG-3, while in Treg cells a reduction of CTLA-4+ cells was seen in response to the adipocyte supernatant. Overall, HFD changes the inflammatory phenotype of a HDM-induced AAI only in association with weight gain and related inflammatory processes in the obese adipose tissue. Further, the expression of co-inhibitory receptors PD-1, CTLA-4, and LAG-3 on CD4+ T cells, which may represent a putative disease-limiting mechanism, was observed in response to the induction of AAI only in lean mice. However, the absence of CD4+ T cells expressing such receptors might in turn underlie altered and potentially aggravated and/or prolonged inflammatory processes in obese HDM-exposed mice. By demonstrating obesity-mediated alterations of the AAI phenotype and the identification of putative immune mechanisms behind this observation, these findings provide significant deeper insights into the specific pathophysiology of obesity-associated asthma with implications for the development of stratified therapy concepts for this disease condition

Difference and Dominance between East and West: A Plea for a Nationwide Reappraisal of the German Unification and Transformation

There are now thirty years since the fall of the Berlin Wall and the German unification. A whole generation has since then grown up in Germany, who knows the period of division only from history books. The subject of German division should be over and done with by now – should it not? The current developments in Germany would indicate otherwise. Among these developments, the success of the party Alternative für Deutschland (AfD) in state elections has reminded us that significant differences persist between Eastern and Western Germany. This current finding is only an outward manifestation, however, of the dissatisfaction with the process of unification that still persists on the part of many East Germans. For a long time, little was heard on the topic in the public sphere, but it is still current and must be addressed publicly lest further potential social conflicts develop from it. The thesis of the present article is that the current differences between East and West Germans1 can no longer be explained merely by differences in socialization before 1989, but are also the manifestation of a West German culture of dominance arising in the course of the German unification and the ensuing process of transformation. This culture of dominance is based, as we will show in detail in the following, on a combination of economic, political and cultural dimensions. To examine this complex, I will draw on Rommelspacher’s (1995) concept of dominance culture

The Journeys of Humboldt: A Guide to Efrain Oscher’s Composition for Orchestra

The purpose of this monograph is to provide a conductor’s guide to the preparation, performance, and programing of Efrain Oscher’s composition for orchestra “Los Viajes de Humboldt” since there has been no other research done on this composition. This monograph offers a biography of the composer and an insight into the composer’s intentions and thoughts when composing this piece. The following monograph also provides a better understanding of the historical context of this piece by detailing the journey of Alexander von Humboldt to the Americas, in particular, his experiences of his time spent in Venezuela from 1799 to 1800. Moreover, this research delves into the life and paintings of Ferdinand Bellermann from the 1840s, paintings that also inspired this composition. The following research aims to provide a guide into programming this piece and to provide an in-depth analysis of the piece. This monograph aspires to serve in future studies of this piece and to help fellow conductors, performers, musicologists, and theorists who are interested in this piece

Power of Perspective: The Effects of Public Perceptions of Police and Fear of Crime on Attitudes Towards Aerial Drone Use

Historically, unmanned aerial systems (UAS; i.e., drones) have largely been used by the military and federal government. As UAS have become more affordable and easier to operate in recent years, state and local law enforcement agencies have become interested in adopting this technology to facilitate a wide range of police activities (e.g., search and rescue, surveillance, tactical operations, etc.). The Federal Aviation Administration (FAA) has begun to regulate the use of unmanned aerial systems, which will likely lead to the increased use of drone technology by law enforcement agencies across the country in upcoming years. However, previous research suggests that public perception of UAS use by the police is mixed, and in some cases there is considerable resistance to police departments adopting this technology. In the present research, we explore several personality factors related to public attitudes towards police UAS use. More specifically, we conducted a national survey examining the relationship between public perceptions of police legitimacy and effectiveness, as well as fear of crime and victimization, and police use of drone technology. The potential implications for public policy and law enforcement practices, particularly in terms of the introduction of UAS into local communities, are discussed

Taking on the Unknown: A Qualitative Comparative Analysis of Unknown Relationship Homicides

Aside from noting the dramatic rise in their numbers, homicides with unknown victim/offender relationships have attracted little research attention. This study uses Qualitative Comparative Analysis and data from the Supplementary Homicide Reports for 1976 through 1998 to examine the nature of unknown relationship homicides and changes in their structure over time. The findings indicate that a large number of unknown relationship cases are contained within a few prevalent homicide situations while also occurring in a diverse array of less common situations. The situational context of unknown homicides exhibits considerable change over time, shifting from the killing of older White males with a variety of weapons to killings involving young Black males with guns. Although unknown and stranger homicides frequently share common structures, they demonstrate notable differences as well, suggesting that unknown relationships cannot automatically be assumed to involve strangers. Implications of the findings for policy and future research are discussed

Burglary trends in Nevada, 1990-2007

Burglary involves the unlawful breaking and entering into a home or other building with the intent to steal something within it. Nationally, about 2.2 million burglaries were known to the police in 2007 (UCR, 2007). Over the last two decades, Nevada’s burglary rate is consistently higher than the national average. There are many consequences of burglary as well as efforts to control these offenses. The presentation of this state data brief describes patterns of burglary in Nevada and compares them with national trends. It examines the prevalence of burglary over time, the different types of burglary and its offense attributes, and arrest characteristics for this crime