Mechanismen der Kontaktaktivierung während einer Infektion mit Streptococcus pyogenes

Das humane Kontaktsystem aktiviert sowohl Blutgerinnung als auch Entzündung. Wie ich im Rahmen meiner Studien erstmalig gezeigt habe, kann die Aktivierung des Systems durch die Bakterien selbst als auch durch Wirtsstrukturen, die als Antwort auf die Bakterien freigesetzt werden, erfolgen. So unterstützt das Kontaktsystems während einer Infektion die Aktivierung der lokalen angeborenen Immunantwort. Andererseits haben pathogene Bakterien Mechanismen entwickelt Kontaktfaktoren zu aktivieren, was mit einer erhöhten Virulenz einhergeht.The human contact system activates both coagulation and inflammation. As I showed for the first time in my studies, the system can be activated by the bacteria themselves as well as by host structures that are released in response to the bacteria. The role of the contact system during an infection appears ambiguous, because on the one hand the activation on the surface of bacteria supports the local innate immune response. On the other hand, pathogenic bacteria in particular have developed mechanisms to activate contact factors, which is associated with increased virulence

Predicting urban tree cover from incomplete point labels and limited background information

Trees inside cities are important for the urban microclimate, contributing positively to the physical and mental health of the urban dwellers. Despite their importance, often only limited information about city trees is available. Therefore in this paper, we propose a method for mapping urban trees in high-resolution aerial imagery using limited datasets and deep learning. Deep learning has become best-practice for this task, however, existing approaches rely on large and accurately labelled training datasets, which can be difficult and expensive to obtain. However, often noisy and incomplete data may be available that can be combined and utilized to solve more difficult tasks than those datasets were intended for. This paper studies how to combine accurate point labels of urban trees along streets with crowd-sourced annotations from an open geographic database to delineate city trees in remote sensing images, a task which is challenging even for humans. To that end, we perform semantic segmentation of very high resolution aerial imagery using a fully convolutional neural network. The main challenge is that our segmentation maps are sparsely annotated and incomplete. Small areas around the point labels of the street trees coming from official and crowd-sourced data are marked as foreground class. Crowd-sourced annotations of streets, buildings, etc. define the background class. Since the tree data is incomplete, we introduce a masking to avoid class confusion. Our experiments in Hamburg, Germany, showed that the system is able to produce tree cover maps, not limited to trees along streets, without providing tree delineations. We evaluated the method on manually labelled trees and show that performance drastically deteriorates if the open geographic database is not used

Attention as Activation

Activation functions and attention mechanisms are typically treated as having different purposes and have evolved differently. However, both concepts can be formulated as a non-linear gating function. Inspired by their similarity, we propose a novel type of activation units called attentional activation (ATAC) units as a unification of activation functions and attention mechanisms. In particular, we propose a local channel attention module for the simultaneous non-linear activation and element-wise feature refinement, which locally aggregates point-wise cross-channel feature contexts. By replacing the well-known rectified linear units by such ATAC units in convolutional networks, we can construct fully attentional networks that perform significantly better with a modest number of additional parameters. We conducted detailed ablation studies on the ATAC units using several host networks with varying network depths to empirically verify the effectiveness and efficiency of the units. Furthermore, we compared the performance of the ATAC units against existing activation functions as well as other attention mechanisms on the CIFAR-10, CIFAR-100, and ImageNet datasets. Our experimental results show that networks constructed with the proposed ATAC units generally yield performance gains over their competitors given a comparable number of parameters

Extracellular aspartic protease SAP2 of Candida albicans yeast cleaves human kininogens and releases proinflammatory peptides, Met-Lys-bradykinin and des-Arg(9)-Met-Lys-bradykinin

Bradykinin-related peptides, universal mediators of inflammation collectively referred to as the kinins, are often produced in excessive amounts during microbial infections. We have recently shown that the yeast Candida albicans, the major fungal pathogen to humans, can exploit two mechanisms to enhance kinin levels at the sites of candidial infection, one depending on adsorption and activation of the endogenous kinin-generating system of the host on the fungal cell wall and the other relying on cleavage of kinin precursors, the kininogens, by pathogen-secreted proteases. This work aimed at assigning this kininogenase activity to the major secreted aspartic protease of C. albicans (SAP2). The purified SAP2 was shown to cleave human kininogens, preferably the low molecular mass form (LK) and optimally in an acidic environment (pH 3.5-4.0), and to produce two kinins, Met-Lys-bradykinin and its derivative, {[}Hydroxyproline(3)]-Met-Lys-bradykinin, both of which are capable of interacting with cellular bradykinin receptors of the B2 subtype. Additionally, albeit with a lower yield, des-Arg(9)-Met-Lys-bradykinin, an effective agonist of B1-subtype receptors, was released. The pathophysiological potential of these kinins and des-Arg-kinin was also proven by presenting their ability to stimulate human promonocytic cells U937 to release proinflammatory interleukin 1 beta (IL-1 beta) and IL-6

Cleavage of Kininogen and Subsequent Bradykinin Release by the Complement Component: Mannose-Binding Lectin-Associated Serine Protease (MASP)-1

Bradykinin (BK), generated from high-molecular-weight kininogen (HK) is the major mediator of swelling attacks in hereditary angioedema (HAE), a disease associated with C1-inhibitor deficiency. Plasma kallikrein, activated by factor XIIa, is responsible for most of HK cleavage. However other proteases, which activate during episodes of angioedema, might also contribute to BK production. The lectin pathway of the complement system activates after infection and oxidative stress on endothelial cells generating active serine proteases: MASP-1 and MASP-2. Our aim was to study whether activated MASPs are able to digest HK to release BK. Initially we were trying to find potential new substrates of MASP-1 in human plasma by differential gel electrophoresis, and we identified kininogen cleavage products by this proteomic approach. As a control, MASP-2 was included in the study in addition to MASP-1 and kallikrein. The proteolytic cleavage of HK by MASPs was followed by SDS-PAGE, and BK release was detected by HPLC. We showed that MASP-1 was able to cleave HK resulting in BK production. MASP-2 could also cleave HK but could not release BK. The cleavage pattern of MASPs is similar but not strictly identical to that of kallikrein. The catalytic efficiency of HK cleavage by a recombinant version of MASP-1 and MASP-2 was about 4.0×102 and 2.7×102 M−1s−1, respectively. C1-inhibitor, the major inhibitor of factor XIIa and kallikrein, also prevented the cleavage of HK by MASPs. In all, a new factor XII- and kallikrein-independent mechanism of bradykinin production by MASP-1 was demonstrated, which may contribute to the pro-inflammatory effect of the lectin pathway of complement and to the elevated bradykinin levels in HAE patients