No abstract

Effluent procalcitonin, IL-13, and RANTES protein levels as well as serum procalcitonin levels correlate with wound dehiscence following closure of severe open extremity wounds. These preliminary results indicate that effluent biomarker analysis may be an objective means of determining the timing of traumatic wound closure.

Protein farnesyltransferase (PFTase) catalyzes the attachment of a geranylazide (C10) or farnesylazide (C15) moiety from the corresponding prenyldiphosphates to a model peptide substrate, N-dansyl-Gly-Cys-Val-Ile-Ala-OH. The rates of incorporation for these two substrate analogs are comparable and approximately twofold lower than that using the natural substrate farnesyl diphosphate (FPP). Reaction of N-dansyl-Gly-Cys(S-farnesylazide)-Val-Ile-Ala-OH with 2-diphenylphosphanylbenzoic acid methyl ester then gives a stable alkoxy-imidate linked product. This result suggests future generations whereby azide groups introduced using this enzymatic approach are functionalized using a broad range of azide-reactive reagents. Thus, chemistry has been developed that could be used to achieve highly specific peptide and protein modification. The farnesylazide analog may be useful in certain biological studies, whereas the geranylazide group may be more useful for general protein modification and immobilization.

Body odour is a characteristic trait of Homo sapiens, however its role in human behaviour and evolution is poorly understood. Remarkably, body odour is linked to the presence of a few species of commensal microbes. Herein we discover a bacterial enzyme, limited to odour-forming staphylococci that are able to cleave odourless precursors of thioalcohols, the most pungent components of body odour. We demonstrated using phylogenetics, biochemistry and structural biology that this cysteinethiol lyase (C-T lyase) is a PLP-dependent enzyme that moved horizontally into a unique monophyletic group of odour-forming staphylococci about 60 million years ago, and has subsequently tailored its enzymatic function to human-derived thioalcohol precursors. Significantly, transfer of this enzyme alone to non-odour producing staphylococci confers odour production, demonstrating that this C-T lyase is both necessary and sufficient for thioalcohol formation. The structure of the C-T lyase compared to that of other related enzymes reveals how the adaptation to thioalcohol precursors has evolved through changes in the binding site to create a constrained hydrophobic pocket that is selective for branched aliphatic thioalcohol ligands. The ancestral acquisition of this enzyme, and the subsequent evolution of the specificity for thioalcohol precursors implies that body odour production in humans is an ancient process. Human body odour is produced by bacterial transformation of odourless precursor molecules secreted onto the surface of the skin by apocrine glands 1-3. These glands are one of two major types of sweat gland found in Homo sapiens, the other being the eccrine glands. Eccrine glands are found in high density all over the body, they open directly onto the surface of the skin and are essential for thermoregulation 4 (Fig. 1A). In contrast, apocrine glands open into hair follicles and typically occur in high density at specific body sites (axilla [underarm], nipple and external genitalia) (Fig. 1A); their exact function and physiological role in modern humans remain poorly understood. The axillary microbiota plays an important role in the generation of human body odour. Staphylococcus, Cutibacterium (formerly Propionibacterium) and Corynebacterium are the dominant genera colonizing the axilla 5,6 , with recent metataxonomic studies highlighting the additional presence of Gram-positive anaerobic cocci (GPAC), notably Anaerococcus and Peptoniphilus species 5,7. Human axillary malodour is comprised of a mixture of volatile organic compounds with volatile fatty acids (VFAs) and thioalcohols being the primary components (Supplementary Information Figure S1) 8-10. Thioalcohols, despite being present in trace amounts, are the most pungent voaltiles 9. Natsch et al. 2,11 identified trace amounts of four different thioalcohols in axillary secretions with 3-methyl-3-sulfanylhexan-1-ol (3M3SH) being the most abundant. 3M3SH is generated from the odourless precursor Cys-Gly-3M3SH, an l-cysteinylglycine dipeptide-conjugated alcohol that is secr...