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Streptococcus pyogenes nuclease A interferes with host complement functions
No full textBacterial pathogens deploy diverse virulence factors to subvert host immunity, yet the molecular details of these interactions often remain unresolved. Here, we investigate the structure and host interactome of the Streptococcus pyogenes nuclease A (SpnA). We characterized the structure and dynamics of SpnA using hydrogen-deuterium exchange mass spectrometry and single-particle electron cryo microscopy, yielding the first structural insights to this protein. This allowed us to identify an additional oligonucleotide-binding domain whose flexible structure may play an important function in the nucleolytic activity of SpnA. Affinity-pulldown mass spectrometry identified the complement system membrane attack complex C5b67 components as key interactors in human plasma. Cross-linking mass spectrometry combined with integrative modeling identified the direct binding interfaces between SpnA and C5b67. These interfaces are highly conserved among genetically diverse S. pyogenes strains. The interaction between SpnA and C5b67 is suggested to prevent the assembly of a functional membrane attack complex. Taken together, our findings uncover a novel function of SpnA in complement inhibition and identifies new potential targets to prevent and treat S. pyogenes infections
Robust Incremental Structure-from-Motion with Hybrid Features
No full textStructure-from-Motion (SfM) has become a ubiquitous tool for camera calibration and scene reconstruction with many downstream applications in computer vision and beyond. While the state-of-the-art SfM pipelines have reached a high level of maturity in well-textured and well-configured scenes over the last decades, they still fall short of robustly solving the SfM problem in challenging scenarios. In particular, weakly textured scenes and poorly constrained configurations oftentimes cause catastrophic failures or large errors for the primarily keypointbased pipelines. In these scenarios, line segments are often abundant and can offer complementary geometric constraints. Their large spatial extent and typically structured configurations lead to stronger geometric constraints as compared to traditional keypoint-based methods. In this work, we introduce an incremental SfM system that, in addition to points, leverages lines and their structured geometric relations. Our technical contributions span the entire pipeline (mapping, triangulation, registration) and we integrate these into a comprehensive end-to-end SfM system that we share as an open-source software with the community. We also present the first analytical method to propagate uncertainties for 3D optimized lines via sensitivity analysis. Experiments show that our system is consistently more robust and accurate compared to the widely used point-based state of the art in SfM – achieving richer maps and more precise camera registrations, especially under challenging conditions. In addition, our uncertainty-aware localization module alone is able to consistently improve over the state of the art under both pointalone and hybrid setups
Selection, characterisation and safety of Limosilactobacillus reuteri DSM 32846, an evolved version of DSM 17938
No full textPredicting probiotic strain properties that translate into beneficial effects in the host is challenging and could be considered the holy grail in developing new probiotics. One approach is to selectively evolve well-studied probiotic strains known to elicit beneficial effects in clinical studies. In this study, Limosilactobacillus reuteri DSM 17938, among the world's most studied probiotic strains, constituted the origin from which the novel strain L. reuteri BG-R46® (DSM 32846) was obtained by exposure to bile, a major stressor of the gastrointestinal tract. The bioactivity of DSM 32846 in preclinical models is documented elsewhere; this work adds crucial strain characteristics, genomic and phenotypic safety profiles, and safety and tolerability in a randomised human study. DSM 32846 was compared to DSM 17938 in terms of tolerance to bile and synthetic gastric juice, with DSM 32846 showing increased bile tolerance and slightly reduced tolerance to gastric pH. Morphological examination by scanning electron microscopy revealed high abundance of extracellular membrane vesicles on the surface of DSM 32846, a previously described bioactive feature of the strain. In addition, the activity of 5-nucleotidase, an adenosine-producing enzyme expressed on the bacterial cell surface and membrane vesicles, was increased in large-scale production batches of DSM 32846 compared to DSM 17938. Phenotypic safety assessment showed that DSM 32846 does not produce any of the evaluated biogenic amines, produces D- and L-lactate with a ratio typical for the species, and lacks haemolytic activity. The minimum inhibitory concentration profile for antibiotics did not raise any safety concerns. A genome safety assessment revealed no antibiotic resistance and virulence genes. DSM 32846 was found safe for human consumption with no differences from the control group in any of the evaluated parameters. In conclusion, L. reuteri DSM 32846 is a safe strain that shows interesting differences to its parent strain DSM 17938
Review of Structural Health Monitoring methods for the assessment of probabilistic models of imposed loads
No full textProbabilistic models of imposed loads require adjustments to reflect current knowledge and experience. To do so, relevant data about their spatial and temporal variability must be collected. Structural Health Monitoring allows to estimate loads acting on bridges by measuring the relevant strains or deflections. Adapting this approach to buildings is not straightforward due to the increased complexity of such systems. This study reviews existing methods and past experiments carried out for buildings and assesses their relevance for estimating the magnitude, position, and duration of loads, establishing a foundation for future laboratory and in-situ tests
A Historic Description of the Department of Geography at Lund University : With special focus on Physical Geography 1880-2000
No full textThis book describes the Department of Physical Geography at Lund University from 1880 to 2000. It focuses on the staff and the development of Geography from its beginnings as a branch of History in 1880 through a period of traditional Geography up to 1948, when the subject was divided into two branches: physical Geography and Human and Economic Geography. Finally, the subject developed into a modern, vital subject focusing on climate change issues during the late 2000th century
Social media communication to create public safety and oppose public fear : Insights into how Swedish public sector organizations convey a sense of public safety via Instagram
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