Browse
Recent Submissions
Now showing 1 - 5 of 577
- ItemCorrecting systematic errors by hybrid 2D correlation loss functions in nonlinear inverse modelling(San Francisco, California, US : PLOS, 2023) Mayerhöfer, Thomas G.; Noda, Isao; Pahlow, Susanne; Heintzmann, Rainer; Popp, JürgenRecently a new family of loss functions called smart error sums has been suggested. These loss functions account for correlations within experimental data and force modeled data to obey these correlations. As a result, multiplicative systematic errors of experimental data can be revealed and corrected. The smart error sums are based on 2D correlation analysis which is a comparably recent methodology for analyzing spectroscopic data that has found broad application. In this contribution we mathematically generalize and break down this methodology and the smart error sums to uncover the mathematic roots and simplify it to craft a general tool beyond spectroscopic modelling. This reduction also allows a simplified discussion about limits and prospects of this new method including one of its potential future uses as a sophisticated loss function in deep learning. To support its deployment, the work includes computer code to allow reproduction of the basic results.
- ItemClonal Complexes Distribution of Staphylococcus aureus Isolates from Clinical Samples from the Caribbean Islands(Basel : MDPI, 2023) Monecke, Stefan; Akpaka, Patrick Eberechi; Smith, Margaret R.; Unakal, Chandrashekhar G.; Thoms Rodriguez, Camille-Ann; Ashraph, Khalil; Müller, Elke; Braun, Sascha D.; Diezel, Celia; Reinicke, Martin; Ehricht, RalfThe aim of this study was to comprehensively characterise S. aureus from the Caribbean Islands of Trinidad and Tobago, and Jamaica. A total of 101 S. aureus/argenteus isolates were collected in 2020, mainly from patients with skin and soft tissue infections. They were characterised by DNA microarray allowing the detection of ca. 170 target genes and assignment to clonal complexes (CC)s and strains. In addition, the in vitro production of Panton–Valentine leukocidin (PVL) was examined by an experimental lateral flow assay. Two isolates were identified as S. argenteus, CC2596. The remaining S. aureus isolates were assigned to 21 CCs. The PVL rate among methicillin-susceptible S. aureus (MSSA) isolates was high (38/101), and 37 of the 38 genotypically positive isolates also yielded positive lateral flow results. The isolate that did not produce PVL was genome-sequenced, and it was shown to have a frameshift mutation in agrC. The high rate of PVL genes can be attributed to the presence of a known local CC8–MSSA clone in Trinidad and Tobago (n = 12) and to CC152–MSSA (n = 15). In contrast to earlier surveys, the USA300 clone was not found, although one MSSA isolate carried the ACME element, probably being a mecA-deficient derivative of this strain. Ten isolates, all from Trinidad and Tobago, were identified as MRSA. The pandemic ST239–MRSA–III strain was still common (n = 7), but five isolates showed a composite SCCmec element not observed elsewhere. Three isolates were sequenced. That showed a group of genes (among others, speG, crzC, and ccrA/B-4) to be linked to its SCC element, as previously found in some CC5– and CC8–MRSA, as well as in S. epidermidis. The other three MRSA belonged to CC22, CC72, and CC88, indicating epidemiological connections to Africa and the Middle East.
- ItemPIEZO1-mediated mechanosensing governs NK cell killing efficiency and infiltration in three-dimensional matrices([Cold Spring Harbor] : Cold Spring Harbor Laboratory (CSHL), 2024) Yanamandra, Archana K.; Zhang, Jingnan; Montalvo, Galia; Zhou, Xiangda; Biedenweg, Doreen; Zhao, Renping; Sharma, Shulagna; Hoth, Markus; Lautenschläger, Franziska; Otto, Oliver; del Campo, Aránzazu; Qu, BinNatural killer (NK) cells play a vital role in eliminating tumorigenic cells. Efficient locating and killing of target cells in complex three-dimensional (3D) environments are critical for their functions under physiological conditions. However, the role of mechanosensing in regulating NK cell killing efficiency in physiologically relevant scenarios is poorly understood. Here, we report that the responsiveness of NK cells is regulated by tumor cell stiffness. NK cell killing efficiency in 3D is impaired against softened tumor cells, while it is enhanced against stiffened tumor cells. Notably, the durations required for NK cell killing and detachment are significantly shortened for stiffened tumor cells. Furthermore, we have identified PIEZO1 as the predominantly expressed mechanosensitive ion channel among the examined candidates in NK cells. Perturbation of PIEZO1 abolishes stiffness-dependent NK cell responsiveness, significantly impairs the killing efficiency of NK cells in 3D, and substantially reduces NK cell infiltration into 3D collagen matrices. Conversely, PIEZO1 activation enhances NK killing efficiency as well as infiltration. In conclusion, our findings demonstrate that PIEZO1-mediated mechanosensing is crucial for NK killing functions, highlighting the role of mechanosensing in NK cell killing efficiency under 3D physiological conditions and the influence of environmental physical cues on NK cell functions.
- ItemImpact of mucus modulation by N-acetylcysteine on nanoparticle toxicity(Amsterdam : Elsevier, 2023) Meziu, Enkeleda; Shehu, Kristela; Koch, Marcus; Schneider, Marc; Kraegeloh, AnnetteHuman respiratory mucus is a biological hydrogel that forms a protective barrier for the underlying epithelium. Modulation of the mucus layer has been employed as a strategy to enhance transmucosal drug carrier transport. However, a drawback of this strategy is a potential reduction of the mucus barrier properties, in particular in situations with an increased exposure to particles. In this study, we investigated the impact of mucus modulation on its protective role. In vitro mucus was produced by Calu-3 cells, cultivated at the air-liquid interface for 21 days and used for further testing as formed on top of the cells. Analysis of confocal 3D imaging data revealed that after 21 days Calu-3 cells secrete a mucus layer with a thickness of 24 ± 6 μm. Mucus appeared to restrict penetration of 500 nm carboxyl-modified polystyrene particles to the upper 5–10 μm of the layer. Furthermore, a mucus modulation protocol using aerosolized N-acetylcysteine (NAC) was developed. This treatment enhanced the penetration of particles through the mucus down to deeper layers by means of the mucolytic action of NAC. These findings were supported by cytotoxicity data, indicating that intact mucus protects the underlying epithelium from particle-induced effects on membrane integrity. The impact of NAC treatment on the protective properties of mucus was probed by using 50 and 100 nm amine-modified and 50 nm carboxyl-modified polystyrene nanoparticles, respectively. Cytotoxicity was only induced by the amine-modified particles in combination with NAC treatment, implying a reduced protective function of modulated mucus. Overall, our data emphasize the importance of integrating an assessment of the protective function of mucus into the development of therapy approaches involving mucus modulation.
- ItemHuman glabrous skin contains crystallized urea dendriform structures in the stratum corneum which affect the hydration levels(Oxford : Wiley-Blackwell, 2023) Infante, Victor Hugo Pacagnelli; Bennewitz, Roland; Kröger, Marius; Meinke, Martina C.; Darvin, Maxim E.Glabrous skin is hair-free skin with a high density of sweat glands, which is found on the palms, and soles of mammalians, covered with a thick stratum corneum. Dry hands are often an occupational problem which deserves attention from dermatologists. Urea is found in the skin as a component of the natural moisturizing factor and of sweat. We report the discovery of dendrimer structures of crystalized urea in the stratum corneum of palmar glabrous skin using laser scanning microscopy. The chemical and structural nature of the urea crystallites was investigated in vivo by non-invasive techniques. The relation of crystallization to skin hydration was explored. We analysed the index finger, small finger and tenar palmar area of 18 study participants using non-invasive optical methods, such as laser scanning microscopy, Raman microspectroscopy and two-photon tomography. Skin hydration was measured using corneometry. Crystalline urea structures were found in the stratum corneum of about two-thirds of the participants. Participants with a higher density of crystallized urea structures exhibited a lower skin hydration. The chemical nature and the crystalline structure of the urea were confirmed by Raman microspectroscopy and by second harmonic generated signals in two-photon tomography. The presence of urea dendrimer crystals in the glabrous skin seems to reduce the water binding capacity leading to dry hands. These findings highlight a new direction in understanding the mechanisms leading to dry hands and open opportunities for the development of better moisturizers and hand disinfection products and for diagnostic of dry skin.