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Pingel, J.

Publications and source records attributed to Pingel, J..

2 recordsLinked to original sources

Antibody Correlates of Resilience to Staphylococcus aureus Disease and Recurrence in Children

Staphylococcus aureus remains a major global pathogen with no licensed vaccine and high recurrent infection burden, yet correlates of protection remain undefined. In a prospective pediatric cohort, we profiled 319 children spanning non-carriers, asymptomatic carriers, those with skin and soft tissue infection (SSTI), or invasive disease. We interrogated 182,149 antibody features, generating the most comprehensive S. aureus immune profiling dataset to date. Antibody responses increased with age, marked by expansion of IgG subclasses and Fc-receptor engagement. Asymptomatic carriage was associated with functional antibody profiles targeting conserved surface antigens and select toxins. Multivariate modeling robustly distinguished clinical phenotypes and identified high-value antigens associated with disease resilience. Protection from recurrent disease converged on enhanced Fc{gamma}R binding and antibody effector function. These findings nominate key antigen targets, and highlight anti-Hla neutralizing antibodies and functional antibodies to additional surface antigens that can be recapitulated through Fc engineering, informing next-generation vaccine and monoclonal antibody strategies.

immunology↗

Mapping 3D tissue orientation with tensor-augmented light-sheet microscopy

Mapping the three-dimensional directional organization of biological tissues is essential for understanding their structure and function. However, existing methods cannot resolve micrometer-scale orientation in volumetric samples. We introduce tensor light-sheet scattering microscopy (tLSSM), a label-free method that reconstructs 3D fiber orientations at micrometer resolution in optically cleared tissues, enabling whole-organ imaging. We discovered that even in transparent samples, organized structures such as neural fibers scatter light in directional patterns, consistent with models of light scattering by cylinders. We compared tLSSM against diffusion MRI in the mouse brain, demonstrating strong agreement and orders of magnitude superior spatial resolution. Furthermore, we showcase tLSSMs versatility across diverse contexts, including whole-brain label-free tracing, pathological demyelination lesions, heart tissue, peripheral nerves, and human white matter. By enabling whole-organ fiber orientation mapping compatible with standard light-sheet microscopes, tLSSM establishes a new standard for mesoscopic connectivity studies by mapping tissue architecture beyond the limits of traditional sectioning.

neuroscience↗