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Sauer, K.

Publications and source records attributed to Sauer, K..

3 recordsLinked to original sources

Alginate hydrogels loaded with pyruvate dehydrogenase enzyme: a novel wound dressing to disassemble Pseudomonas aeruginosa biofilm

Topical wounds require effective dressings to manage wound exudate, maintain moisture, and avoid infection. Alginate hydrogels are widely used clinically due to their biocompatibility, high absorbency, and ability to maintain a moist wound environment during healing; however, alginate can also promote bacterial biofilm formation and prolong healing. Depleting pyruvate using the enzyme pyruvate dehydrogenase (PDH) has been shown in both in vitro and in vivo studies to effectively disrupt biofilm structure. This study entraps PDH in alginate hydrogels to disperse/disassemble biofilms formed by a prevalent wound pathogen, Pseudomonas aeruginosa. PDH depletes pyruvate and alters the biofilm metabolism, resulting in the prevention and dispersion of biofilms. Alginate hydrogels exhibited compressive moduli ranging from 15 to 80 kPa, with the water content of all swollen hydrogels exceeding 90%, and demonstrated structural stability in simulated wound exudate. PDH loading of 0.85 U in 65 {micro}l of alginate achieved maximum observed enzymatic activity, 60% of which was retained after six days. Notably, PDH-loaded hydrogels significantly reduced biofilm biomass by 40.94% {+/-} 6.07 compared to media alone and by 80.05% {+/-} 6.37 compared to the Dimora(R) commercial alginate dressing. Furthermore, PDH-entrapped alginate hydrogels significantly reduce biofilm biomass without affecting the viability of human dermal fibroblasts, highlighting the commercial potential of the material. The successful integration of a biofilm metabolism-altering enzyme within wound dressings presents a promising avenue for improving chronic wound management and reducing the burden of biofilm-associated infections without the need for the discovery of new antibiotic drugs. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=149 SRC="FIGDIR/small/661844v1_ufig1.gif" ALT="Figure 1"> View larger version (49K): org.highwire.dtl.DTLVardef@1fe58bforg.highwire.dtl.DTLVardef@1748051org.highwire.dtl.DTLVardef@19453eborg.highwire.dtl.DTLVardef@111a9b6_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

Allelic variation in Class I HLA determines pre-existing memory responses to SARS-CoV-2 that shape the CD8+ T cell repertoire upon viral exposure

Effective presentation of antigens by HLA class I molecules to CD8+ T cells is required for viral elimination and generation of long-term immunological memory. In this study, we applied a single-cell, multi-omic technology to generate the first unified ex vivo characterization of the CD8+ T cell response to SARS-CoV-2 across 4 major HLA class I alleles. We found that HLA genotype conditions key features of epitope specificity, TCR /{beta} sequence diversity, and the utilization of pre-existing SARS-CoV-2 reactive memory T cell pools. Single-cell transcriptomics revealed functionally diverse T cell phenotypes of SARS-CoV-2-reactive T cells, associated with both disease stage and epitope specificity. Our results show that HLA variations influence pre-existing immunity to SARS-CoV-2 and shape the immune repertoire upon subsequent viral exposure. One-Sentence SummaryWe perform a unified, multi-omic characterization of the CD8+ T cell response to SARS-CoV-2, revealing pre-existing immunity conditioned by HLA genotype.

immunology↗

Common functional networks in the mouse brain revealed by multi-centre resting-state fMRI analysis

Preclinical applications of resting-state functional magnetic resonance imaging (rsfMRI) offer the possibility to non-invasively probe whole-brain network dynamics and to investigate the determinants of altered network signatures observed in human studies. Mouse rsfMRI has been increasingly adopted by numerous laboratories world-wide. Here we describe a multi-centre comparison of 17 mouse rsfMRI datasets via a common image processing and analysis pipeline. Despite prominent cross-laboratory differences in equipment and imaging procedures, we report the reproducible identification of several large-scale resting-state networks (RSN), including a murine default-mode network, in the majority of datasets. A combination of factors was associated with enhanced reproducibility in functional connectivity parameter estimation, including animal handling procedures and equipment performance. Our work describes a set of representative RSNs in the mouse brain and highlights key experimental parameters that can critically guide the design and analysis of future rodent rsfMRI investigations.

neuroscience↗