Biology subjects

Young, S.

Publications and source records attributed to Young, S..

3 recordsLinked to original sources

bioRxiv2018

Validation of a low-cost, carbon dioxide-based cryoablation system for percutaneous tumor ablation

Breast cancer rates are rising in low- and middle-income countries (LMICs), yet there is a lack of accessible and cost-effective treatment. As a result, the cancer burden and death rates are highest in LMICs. In an effort to meet this need, our work presents the design and feasibility of a low-cost cryoablation system using widely-available carbon dioxide as the only consumable. This system uses an 8-gauge outer-diameter needle and Joule-Thomson expansion to percutaneously necrose tissue with cryoablation. Bench top experiments characterized temperature dynamics in ultrasound gel demonstrated that isotherms greater than 2 cm were formed. Further, this system was applied to mammary tumors in an in vivo rat model and necrosis was verified by histopathology. Finally, freezing capacity under a large heat load was assessed with an in vivo porcine study, where volumes of necrosis greater than 1.5 cm in diameter confirmed by histopathology were induced in a highly perfused liver after two 7-minute freeze cycles. These results demonstrate the feasibility of a carbon-dioxide based cryoablation system for improving solid tumor treatment options in resource-constrained environments.

bioengineering↗

bioRxiv2018

Aberrant mast cell activation promotes chronic recurrent multifocal osteomyelitis

Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disease. While some patients exhibit bone lesions at single sites, most patients develop chronically active or recurrent bone inflammation at multiple sites, and are then diagnosed with recurrent multifocal osteomyelitis (CRMO). Chronic multifocal osteomyelitis (CMO) mice develop IL-1{beta}-driven sterile bone lesions reminscent of severe CRMO. Mechanistically, CMO disease arises due to loss of PSTPIP2, a negative regulator of macrophages, osteoclasts and neutrophils. The goal of this study was to evaluate the potential involvement of mast cells in CMO/CRMO disease pathophysiology. Here, we show that mast cells accumulate in the inflamed tissues from CMO mice, and mast cell protease Mcpt1 was detected in the peripheral blood. The role of mast cells in CMO disease was investigated using a transgenic model of connective tissue mast cell depletion (Mcpt5-Cre:Rosa26-Stopfl/fl-DTa) that was crossed with CMO mice. The resulting CMO/MC-mice showed a significant delay in disease onset compared to age-matched CMO mice. At 5-6 months of age, CMO/MC- mice had fewer bone lesions and immune infiltration in the popliteal lymph nodes that drain the affected tail and paw tissues. To test the relevance of mast cells to human CRMO, we tested serum samples from a cohort of healthy controls or CRMO patients at diagnosis. Interestingly, mast cell chymase was elevated in CRMO patients as well as patients with oligoclonal juvenile arthritis. Tryptase-positive mast cells were also detected in bone lesions from CRMO patients as well as patients with bacterial osteomyelitis. Taken together, our results identify mast cells as cellular contributors to bone inflammation in CMO/CRMO. Observations of this study promise potential for mast cells and derived mediators as future biomarkers and/or therapeutic targets.

immunology↗

bioRxiv2018

Whole genome analysis illustrates global clonal population structure of the ubiquitous dermatophyte pathogen Trichophyton rubrum

Dermatophytes include fungal species that infect humans, as well as those which also infect other animals or only grow in the environment. The dermatophyte species Trichophyton rubrum is a frequent cause of skin infection in immunocompetent individuals. While members of the T. rubrum species complex have been further categorized based on various morphologies, the population structure and ability to undergo sexual reproduction are not well understood. In this study, we analyze a large set of T. rubrum and Trichophyton interdigitale isolates to examine mating types, evidence of mating, and genetic variation. We find that nearly all isolates of T. rubrum are of a single mating type, and that incubation with T. rubrum morphotype megninii isolates of the other mating type failed to induce sexual development. While the region around the mating type locus is characterized by a higher frequency of SNPs compared to other genomic regions, we find that the population is remarkably clonal, with highly conserved gene content, low levels of variation, and little evidence of recombination These results support a model of recent transition to asexual growth when this species specialized to growth on human hosts.\n\nData access: Genome sequence data is available in NCBI under the Umbrella BioProject PRJNA186851.

genetics↗