No abstract

Burn wound progression is complex and caused by additive effects of inadequate tissue perfusion, free radical damage, and systemic alterations in the cytokine milieu of burn patients, leading to protein denaturation and necrosis. Even though insufficient evidence exists for causal inferences, infection, tissue desiccation, edema, circumferential eschar, impaired wound perfusion, metabolic derangements, advanced age, and poor general health play important roles. Although consensus-building research is ongoing, current mainstays of treatment include adequate fluid resuscitation, nutritional support, and local wound care, with an emphasis on topical antimicrobial agents and biosynthetic dressings. Identifying early indicators by elucidating possible interacting or synergistic mechanisms and by developing preventative strategies will enhance prevention and treatment.

SummaryFlhB, an integral membrane protein, gates the type III flagellar export pathway of Salmonella . It permits export of rod/hook-type proteins before hook completion, whereupon it switches specificity to recognize filament-type proteins. The cytoplasmic C-terminal domain of FlhB (FlhB C ) is cleaved between Asn-269 and Pro-270, defining two subdomains: FlhB CN and FlhB CC . Here, we show that subdomain interactions and cleavage within FlhB are central to substratespecificity switching. We found that deletions between residues 216 and 240 of FlhB CN permitted FlhB cleavage but abolished function, whereas a deletion spanning Asn-269 and Pro-270 abolished both. The mutation N269A prevented cleavage at the Flh-B CN -FlhB CC boundary. Cells producing FlhB(N269A) exported the same amounts of hook-capping protein as cells producing wild-type FlhB. However, they exported no flagellin, even when the fliC gene was being expressed from a foreign promoter to circumvent regulation of expression by FlgM, which is itself a filament-type substrate. Electron microscopy revealed that these cells assembled polyhook structures lacking filaments. Thus, FlhB(N269A) is locked in a conformation specific for rod/hook-type substrates. With FlhB(P270A), cleavage was reduced but not abolished, and cells producing this protein were weakly motile, exported reduced amounts of flagellin and assembled polyhook filaments.

Microwave ablation with a novel device results in consistently sized and shaped lesions. Importantly, we did not observe any significant heat-sink effect using this device, a major difference from RFA techniques. This system offers a viable alternative for creating fast, large ablation volumes for treatment in liver cancer.