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Poke Weed Mitogen Requires Toll-Like Receptor Ligands for Proliferative Activity in Human and Murine B Lymphocytes
Isabelle Bekeredjian-Ding, Sandra Foermer, Carsten J. Kirschning, Marijo Parcina, Klaus Heeg
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0029806
Abstract: Poke weed mitogen (PWM), a lectin purified from Phytolacca americana is frequently used as a B cell-specific stimulus to trigger proliferation and immunoglobulin secretion. In the present study we investigated the mechanisms underlying the B cell stimulatory capacity of PWM. Strikingly, we observed that highly purified PWM preparations failed to induce B cell proliferation. By contrast, commercially available PWM preparations with B cell activity contained Toll-like receptor (TLR) ligands such as TLR2-active lipoproteins, lipopolysaccharide and DNA of bacterial origin. We show that these microbial substances contribute to the stimulatory activity of PWM. Additional experimental data highlight the capacity of PWM to enable B cell activation by immunostimulatory DNA. Based on these findings we propose that the lectin sensitizes B cells for TLR stimulation as described for B cell receptor ligation and that B cell mitogenicity of PWM preparations results from synergistic activity of the poke weed lectin and microbial TLR ligands present in the PWM preparations.
Regulation of Toll-like receptor 4-mediated immune responses through Pasteurella multocida toxin-induced G protein signalling
Dagmar Hildebrand, Aline Sahr, Sabine J W？lfle, Klaus Heeg, Katharina F Kubatzky
Cell Communication and Signaling , 2012, DOI: 10.1186/1478-811x-10-22
Abstract: Here we show that the activation of heterotrimeric G proteins through PMT suppresses LPS-stimulated IL-12p40 production and eventually impairs the T cell-activating ability of LPS-treated monocytes. This inhibition of TLR4-induced IL-12p40 expression is mediated by Gαi-triggered signalling as well as by Gβγ-dependent activation of PI3kinase and JNK.Taken together we propose the following model: LPS stimulates TLR4-mediated activation of the NF？B-pathway and thereby the production of TNF-α, IL-6 and IL-12p40. PMT inhibits the production of IL-12p40 by Gαi-mediated inhibition of adenylate cyclase and cAMP accumulation and by Gβγ-mediated activation of PI3kinase and JNK activation.On the basis of the experiments with PMT this study gives an example of a pathogen-induced interaction between G protein-mediated and TLR4-triggered signalling and illustrates how a bacterial toxin is able to interfere with the host’s immune response.Monocytes are professional antigen presenting cells and carry out at least two important functions during infection. First of all they represent a barrier against pathogens through their antimicrobial activity and second they support the initiation of adaptive immune responses. The latter is exerted by the presentation of processed antigens on major histocompatibility complex (MHC) molecules to T lymphocytes, the expression of various costimulatory proteins on the cell surface and the production of cytokines [1,2]. To direct these functions during an immune response, monocytes become activated through binding of conserved microbial structures to their respective pattern-recognition receptors (PRRs). Within the group of PRRs, Toll like receptors (TLRs) play a well-known role in the initiation of such immune responses. Up to now, 10 functional TLRs have been identified in humans [3]. Each TLR detects distinct PAMPs derived from viruses, bacteria, mycobacteria, fungi, and parasites [3]. Gram-negative bacteria are typically sensed through the cell wa
The haematopoietic GTPase RhoH modulates IL3 signalling through regulation of STAT activity and IL3 receptor expression
Mehtap S Gündogdu, He Liu, Daniela Metzdorf, Dagmar Hildebrand, Michael Aigner, Klaus Aktories, Klaus Heeg, Katharina F Kubatzky
Molecular Cancer , 2010, DOI: 10.1186/1476-4598-9-225
Abstract: Using the murine IL3-dependent cell line BaF3 we investigated the influence of RhoH protein expression levels on IL3-mediated cellular responses. RhoH overexpressing cells showed lower sensitivity to IL3 and decreased STAT5 activation. SiRNA-mediated repression of RhoH gene expression led to an increase in proliferation and STAT5 activity which correlated with an increased number of IL3 receptor α chain molecules, also known as CD123, expressed at the cell surface. Interestingly, these findings could be reproduced using human THP-1 cells as a model system for acute myeloid leukaemia, where low RhoH levels are known to be an unfavourable prognostic marker. Overexpression of RhoH on the other hand caused an induction of STAT1 activity and western blot analysis revealed that activated STAT1 is phosphorylated on Tyr701. STAT1 is known to induce apoptosis or cell cycle arrest and we detected an upregulation of cyclin-dependent kinase inhibitors (CDKI) p21Cip1 and p27Kip1 in RhoH overexpressing BaF3 cells.We propose that RhoH functions as a negative regulator for IL3-induced signals through modulation of the JAK-STAT pathway. High levels of RhoH allow the IL3-dependent activation of STAT1 causing decreased proliferation through upregulation of p21Cip1 and p27Kip1. Low RhoH levels on the other hand led to an upregulation of IL3-dependent cell growth, STAT5 activity and an increase of CD123 surface expression, linking RhoH to a CD123/STAT5 phenotype that has been described in AML patients.Rho GTPases belong to the superfamily of Ras GTPases [1] and function as molecular switches that control and integrate signal transduction pathways by linking receptor-derived signals to downstream signalling proteins [2-4]. The Rho subfamily of GTPases consists of 20 proteins, but only two members, Rac2 and RhoH, are specifically expressed in haematopoietic cells [5,6]. RhoH is a GTPase deficient protein [7,8] and its activity is presumably modulated through transcriptional regulation [7]
Physische Gewalt als Quelle positiver Selbstwahrnehmung bei jugendlichen M dchen Physical Violence as a Source of Positive Self-perception for Adolescent Girls La violencia física como una fuente de autopercepción positiva para adolescentes
Rahel Heeg
Forum : Qualitative Social Research , 2012,
Abstract: Gewaltausübung durch weibliche Jugendliche ist insbesondere im deutschsprachigen Raum vergleichsweise wenig untersucht. In diesem Artikel werden ausgew hlte Ergebnisse einer Schweizer Studie vorgestellt. 21 weibliche Jugendliche, welche regelm ig physische Gewalt ausüb(t)en, wurden in problemzentrierten Interviews befragt. Die Erhebung und Auswertung der Interviews orientierte sich an der Grounded-Theory-Methodologie. Im Mittelpunkt des Forschungsinteresses stand die Frage, welche Bedeutung ihr eigenes Gewalthandeln für die befragten M dchen hat. Dabei zeigte sich, dass dieses sich je nach der Beziehung der M dchen zu ihren Eltern unterscheidet. Im Mittelpunkt des vorliegenden Beitrags stehen diejenigen weiblichen Jugendlichen, welche von einer engen und positiven Beziehung zu ihren Eltern erz hlen. Es wird anhand zweier Fallbeispiele aufgezeigt, dass Gewaltausübung für diese M dchen eine Quelle positiver Selbstwahrnehmung ist. In Gewaltsituationen fühlen sie sich stark und unabh ngig. Sie setzen Gewalt aber nur gegen Menschen ein, welche für sie nicht wichtig sind. Gegenüber Personen, welche ihnen viel bedeuten, verhalten sich diese M dchen hingegen sozial angepasst und setzen sich nicht durch. Man kann schlussfolgern, dass ihre Selbstwahrnehmung als stark und unabh ngig auf Gewaltsituationen beschr nkt bleibt. URN: http://nbn-resolving.de/urn:nbn:de:0114-fqs1301226 Little is known about physically violent behavior in female adolescents (especially in German speaking countries). Problem-centered interviews with 21 Swiss girls who regularly use(d) physical violence were conducted. The study is based on grounded theory methodology with which the meaning of violence for the interviewed girls was reconstructed. The focus of the study was to find out how girls with a history of physical violent behavior reflect upon their use of violence against others. Results show that these meanings differ according to the relationship to the parents. The focus of this article is on girls with a close and positive relationship to their parents. Two case studies were selected for this article. Results show that these girls perceive themselves as positive, strong, and independent while using violence. Furthermore, these girls selectively perform violence only against people who are less important to them. In contrast, they comply with rules and expectations from people who are important to them. Therefore, one can conclude that their self-perception of strength and independence is situation-specific. URN: http://nbn-resolving.de/urn:nbn:de:0114-fqs1301226 Poco se sabe sob
Wohnungen als Finanzanlage. Auswirkungen von Responsibilisierung und Finanzialisierung im Bereich des Wohnens Housing as Financial Investment. Effects of Responsibilisation and Financialisation on Housing
Susanne Heeg
s u b u r b a n : zeitschrift für kritische stadtforschung , 2013,
Abstract: Bislang war in deutschen St dten das Wohnen im Eigentum – entweder im Eigenheim oder in der Eigentumswohnung – die Ausnahme. Insbesondere in Gro st dten dominierte das Wohnen zur Miete. Gegenw rtig ndert sich dies: Gro st dte wie Frankfurt, Berlin, Hamburg, K ln und München sind gegenw rtig gepr gt von einer Kauflust privater und institutioneller Investoren. Zugleich hat in vielen St dten ein Ausverkauf und/oder Vermarktlichung des ffentlichen Wohnungsbestandes stattgefunden. Dies hat dazu beigetragen, dass die Preise sehr stark angestiegen sind. In dem Beitrag wird die aktuelle Entwicklung auf st dtischen Wohnungsm rkten in Deutschland als Folge einer Finanzialisierung von Immobilien sowie einer Responsibilisierung im Bereich der Wohnversorgung analysiert. Es wird gefragt, welche Folgen dies in St dten hat. Until recently, the housing stock in German cities consisted mostly of rented apartments or rented family homes and not of individually owned residential property. Indeed, residential property was an exception in German cities. This is now going through changes particularly in big cities as Frankfurt, Berlin, Hamburg, Cologne or Munich which are affected by a shopping spree of private and institutional investors alike. At the same time, a selling out respectively marketization of public housing has taken place. This has contributed to massive price increases. I will analyze this development on urban real estate markets as a consequence of the financialisation and responsibilisation of housing and I will address the social and spatial outcomes of these developments in cities.
Heterogeneity of Host TLR2 Stimulation by Staphylocoocus aureus Isolates
Dina Hilmi, Marijo Parcina, Daniel Stollewerk, Jenny Ostrop, Michaele Josten, Alina Meilaender, Ulrich Zaehringer, Thomas A. Wichelhaus, Gabriele Bierbaum, Klaus Heeg, Christiane Wolz, Isabelle Bekeredjian-Ding
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0096416
Abstract: High lipoprotein expression and potent activation of host Toll-like receptor-2 (TLR2) are characteristic features of the staphylococcal species. Expression of TLR2 in the host is important for clearance of Staphylococcus aureus infection and host survival. Thus, we hypothesized that bacterial regulation of its intrinsic TLR2-stimulatory capacity could represent a means for immune evasion or host adaptation. We, therefore, compared clinical S. aureus isolates in regards to their TLR2 activation potential and assessed the bacterial factors that modulate TLR2-mediated recognition. S. aureus isolates displayed considerable variability in TLR2-activity with low to absent TLR2-activity in 64% of the isolates tested (68/106). Notably, strain-specific TLR2-activity was independent of the strain origin, e.g. no differences were found between strains isolated from respiratory specimen from cystic fibrosis patients or those isolated from invasive disease specimen. TLR2-activity correlated with protein A expression but not with the agr status. Capsule expression and small colony variant formation had a negative impact on TLR2-activity but any disruption of cell wall integrity enhanced TLR2 activation. Altogether, heterogeneity in host TLR2-activity reflects differences in metabolic activity and cell wall synthesis and/or remodeling.
X-ray quantum optics with M？ssbauer nuclei embedded in thin film cavities
K. P. Heeg,J. Evers
Physics , 2013, DOI: 10.1103/PhysRevA.88.043828
Abstract: A promising platform for the emerging field of x-ray quantum optics are M\"ossbauer nuclei embedded in thin film cavities probed by near-resonant x-ray light, as used in a number of recent experiments. Here, we develop a quantum optical framework for the description of experimentally relevant settings involving nuclei embedded in x-ray waveguides. We apply our formalism to two settings of current experimental interest based on the archetype M\"ossbauer isotope 57Fe. For present experimental conditions, we derive compact analytical expressions and show that the alignment of medium magnetization as well as incident and detection polarization enable the engineering advanced quantum optical level schemes. The model encompasses non-linear and quantum effects which could become accessible in future experiments.
An Enduring Concept for Security Council Reform  [PDF]
Klaus Schlichtmann
Beijing Law Review (BLR) , 2011, DOI: 10.4236/blr.2011.22010
Abstract: UN Security Council reform has been lingering over the years, since it was first seriously considered in the 1990s, after the collapse of the Soviet Union. This paper argues that enlarging the Security Council by adding new permanent and non-permanent members, while many of the Charter provisions vital for the maintenance of international peace and security and disarmament are not in effect, would be counterproductive. Instead, the composition of the Council should be reshuffled and expanded by giving a seat to a prominent member of the Global South, i.e. India, and replacing the seats of France and Britain with a single European representation. While there would be no increase or change in the number of permanent and non-permanent members, the result will be a dramatic increase in the numbers of people represented by the Permanent Five, which then will, in effect, comprise half of the world’s population projected for 2012. The underlying logic is that increasing the number of permanent members (P5) would make the Security Council not only less effective, but also prevent the realization of a fundamental purpose of the United Nations, i.e. the transition from an armed to an unarmed peace. By maintaining the number 5, the effective operation of the consensus principle required for the maintenance of international peace and security during the transition is ensured. It is maintained that the changes proposed in this paper may be regarded as “purely procedural” under Article 27 paragraph 2 of the Charter. It will be seen, however, that to trigger the process of the transition, UN Member states (other than the P5, who bear responsibility under the Charter to guarantee safe passage during the transition) must begin, one by one, to delegate “Security Sovereignty” to the Council.
Digital Technology to Support the Trade Union Movement  [PDF]
Klaus Schoemann
Open Journal of Social Sciences (JSS) , 2018, DOI: 10.4236/jss.2018.61005
Abstract:
New digital technologies have a potential to bypass traditional forms of labour organization. We summarize the academic and trade union literature on the potential of new digital technologies for trade unions. Building on the literature of the social construction of technology and democracy at work we present the concept of the technology-supported construction of the social sphere. A review of digital technologies allows us to identify the potential innovator role of trade unions and work councils in digital forms of employee participation. Digital technologies are an important way to attract younger generations of trade union members. For experienced members, bridging the digital divide becomes a vital issue, too. Finally, we highlight the active interplay and mutually reinforcing effect of online and offline communication in networking.
Finite-size effects in strongly interacting Rydberg gases
M. G？rttner,K. P. Heeg,T. Gasenzer,J. Evers
Physics , 2012, DOI: 10.1103/PhysRevA.86.033422
Abstract: The scaling of the number of Rydberg excitations in a laser-driven cloud of atoms with the interaction strength is found to be affected by the finite size of the system. The scaling predicted by a theoretical model is compared with results extracted from a numerical many-body simulation. We find that the numerically obtained scaling exponent in general does not agree with the analytical prediction. By individually testing the assumptions leading to the theoretical prediction using the results from the numerical analysis, we identify the origin of the deviations, and explain it as arising from the finite size of the system. Furthermore, finite-size effects in the pair correlation function $g^{(2)}$ are predicted. Finally, in larger ensembles, we find that the theoretical predictions and the numerical results agree, provided that the system is sufficiently homogeneous.
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