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monocytogenes. LUT destroyed the cell membrane integrity, as evidenced by a significant increase in the number of non-viable cells, and well-defined variations in cell morphology. Moreover, LUT presented robust inhibitory effects on the biofilm formation, enhanced antibiotics diffusion within biofilms and killed efficiently mono- and dual-species biofilm cells. Overall, LUT demonstrates potent antimicrobial properties on planktonic and biofilm cells, and the biofilm formation, and thus has the potential use as a natural food preservative in foods. Flavobacterium species are considered important fish pathogens in wild and cultured fish throughout the world. Staurosporine chemical structure They can cause acute, subacute, and chronic infections, which are mainly characterized by gill damage, skin lesions, and deep necrotic ulcerations. Primarily, three Flavobacterium species, F. branchiophilum, F. columnare, and F. psychrophilum, have been reported to cause substantial losses to freshwater fish. In this study, we evaluated genomes of 86 Flavobacterium species isolated from aquatic hosts (mainly fish) to identify their unique and shared genome features. Our results showed that F. columnare genomes cluster into four different genetic groups. In silico secretion system analysis identified that all genomes carry type I (T1SS) and type IX (T9SS) secretion systems, but the number of type I secretion system genes shows diversity between species. F. branchiophilum, F. araucananum, F. chilense, F. spartansii, and F. tructae genomes have full type VI secretion system (T6SS). F. columnare, F. hydatis, and F. plurextorum carry partial T6SS with some of the T6SS genes missing. F. columnare, F. araucananum, F. chilense, F. spartansii, F. araucananum, F. tructae, Flavobacterium sp., F. crassostreae, F. succinicans, F. hydatis, and F. plurextorum carry most of the type IV secretion system genes (T4SS). F. columnare genetic groups 1 and 2, Flavobacterium sp., and F. crassostreae encode the least number of antibiotic resistance elements. F. hydatis, F. chilense, and F. plurextorum encode the greatest number of antibiotic resistance genes. Additionally, F. spartansii, F. araucananum, and chilense encode the greatest number of virulence genes while Flavobacterium sp. and F. crassostreae encode the least number of virulence genes. In conclusion, comparative genomics of Flavobacterium species of aquatic origin will help our understanding of Flavobacterium pathogenesis. Serine protease is the virulence factor of many pathogens. However, there are no prevailing data available for serine protease as a virulence factor derived from Mycobacterium avium subsp. paratuberculosis (MAP). The MAP3292c gene from MAP, the predicted serine protease, was expressed in Escherichia coli and characterized by biochemical methods. MAP3292c protein efficiently hydrolyzed casein at optimal temperature and pH of 41 °C and 9.0, respectively. Furthermore, divalent metal ions of Ca2+ significantly promoted the protease activity of MAP3292c, and MAP3292c had autocleavage activity between serine 86 and asparagine 87. Site-directed mutagenesis studies showed that the serine 238 residue had catalytic roles in MAP3292c. Furthermore, a BALB/c mouse model confirmed that MAP3292c significantly promoted the survival of Mycobacterium smegmatis in vivo; caused damage to the liver, spleen, and lung; and promoted the release of inflammatory cytokines IL-1β, IL-6, and TNF-α in mice. Finally, we confirmed that MAP3292c was relevant to mycobacterial pathogenicity. PURPOSE Diabetes and osteoporosis occur frequently in older adults and are both associated with increased fracture risk. Denosumab treatment reduced new vertebral, nonvertebral, and hip fractures over 3 years, with continued low fracture incidence for up to 10 years in postmenopausal women with osteoporosis. However, its effects in diabetic subjects with osteoporosis have not yet been investigated. METHODS Post hoc analysis of the 3-year, placebo-controlled FREEDOM study and 7-year Extension included postmenopausal women with osteoporosis and diabetes. Effects on BMD, vertebral, and nonvertebral fracture incidence were evaluated. RESULTS Of 7808 subjects in FREEDOM, 508 with diabetes received denosumab (n = 266) or placebo (n = 242). Among those, BMD increased significantly with denosumab versus placebo in FREEDOM, and continued to increase during the Extension in long-term (continuing denosumab) and crossover (placebo to denosumab) denosumab subjects. In FREEDOM, denosumab-treated subjects with diabetes had significantly lower new vertebral fracture rates (1.6%) versus placebo (8.0%) (RR 0.20 [95% CI 0.07-0.61]; p = .001). Nonvertebral fracture incidence was higher with denosumab (11.7%) versus placebo (5.9%) (HR 1.94 [95% CI 1.00-3.77]; p = .046), although there were fewer hip fractures with denosumab (World Health Organization, 2017 [1]) than placebo (4; nonsignificant). During the first 3 years in FREEDOM Extension, new vertebral and nonvertebral fracture incidences were low in long-term and crossover denosumab diabetic groups (≤6%), consistent with the overall Extension population; yearly nonvertebral fracture incidence was comparable to the FREEDOM placebo group. CONCLUSION Denosumab significantly increased BMD and decreased vertebral fracture risk in subjects with osteoporosis and diabetes. No reduction in nonvertebral fractures was observed. In most vertebrates the embryonic cartilaginous skeleton is replaced by bone during development. During this process, cartilage cells (chondrocytes) mineralize the extracellular matrix and undergo apoptosis, giving way to bone cells (osteocytes). In contrast, sharks and rays (elasmobranchs) have cartilaginous skeletons throughout life, where only the surface mineralizes, forming a layer of tiles (tesserae). Elasmobranch chondrocytes, unlike those of other vertebrates, survive cartilage mineralization and are maintained alive in spaces (lacunae) within tesserae. However, the function(s) of the chondrocytes in the mineralized tissue remain unknown. Applying a custom analysis workflow to high-resolution synchrotron microCT scans of tesserae, we characterize the morphologies and arrangements of stingray chondrocyte lacunae, using lacunar morphology as a proxy for chondrocyte morphology. We show that the cell density is comparable in unmineralized and mineralized tissue from our study species and that cells maintain the similar volume even when they have been incorporated into tesserae.