Transglutaminase-2 Mediates the Biomechanical Properties of the Colorectal Cancer Tissue Microenvironment that Contribute to Disease Progression.

Colorectal cancer is the third most common cancer worldwide, and the fourth leading cause of malignancy-related mortality. This highlights the need to understand the processes driving this disease in order to develop new treatments and improve patient outcomes. A potential therapeutic target is the increased stiffness of the tumour microenvironment, which is linked to aggressive cancer cell behaviour by enhancing biomechanical signalling. In this study, we used an siRNA-based approach to investigate the contribution of the protein cross-linking enzyme transglutaminase-2 (TG2) to matrix remodelling and biomechanical properties of the tumour microenvironment. TG2 inhibited cancer cell growth in organotypic 3D fibroblast/SW480 co-culture models, and biomechanical analysis demonstrated that colorectal cancer cells induced fibroblast-mediated stiffness which was inhibited by silencing TG2. These biomechanical changes were associated with observed alterations to collagen fibre structure, notably fibre thickness. Our in vitro findings of collagen composition changes were also seen with imaging biopsied tissues from patients with colorectal cancer, with TG2 correlating positively with thicker collagen fibres, and associating with poor outcome as determined by disease recurrence post-surgery and overall survival. In conclusion, this study demonstrates a role for TG2 in the stromal response to invading tumour, leading to tissue stiffening and poor outcome in patients.

Low pathogenic influenza A virus activity at avian interfaces in Ohio zoos, 2006-2009.

This investigation to examine influenza A virus activity in avian species at four Ohio zoos was initiated to better understand the ecology of avian-origin influenza A (AIV) virus in wild aquatic birds and the possibility of spill-over of such viruses into captive zoo birds, both native and foreign species. Virus isolation efforts resulted in the recovery of three low pathogenic (LP) AIV isolates (one H7N3 and two H3N6) from oral-pharyngeal or cloacal swabs collected from over 1000 zoo birds representing 94 species. In addition, 21 LPAIV isolates possessing H3N6, H4N6, or H7N3 subtype combinations were recovered from 627 (3.3%) environmental fecal samples collected from outdoor habitats accessible to zoo and wild birds. Analysis of oral-pharyngeal and cloacal swabs collected from free-ranging mallards (Anas platyrhynchos) live-trapped at one zoo in 2007 resulted in the recovery of 164 LPAIV isolates (48% of samples) representing five HA and six NA subtypes and at least nine HA-NA combinations. The high frequency of isolate recovery is undoubtedly due to the capture and holding of wild ducks in a common pen before relocation. Serologic analyses using an agar gel immune diffusion assay detected antibodies to the influenza A virus type-specific antigen in 147 of 1237 (11.9%) zoo bird sera and in 14 of 154 (9%) wild mallard sera. Additional analyses of a limited number of zoo bird sera demonstrated HA- and NA-inhibition activity to 15 HA and nine NA subtypes. The spectrum of HA antibodies indicate antibody diversity of AIV infecting zoo birds; however, the contribution of heterologous cross-reactions and steric interference was not ruled out. This proactive investigation documented that antigenically diverse LPAIVs were active in all three components of the avian zoologic-wild bird interfaces at Ohio zoos (zoo birds, the environment, and wild birds). The resulting baseline data provides insight and justification for preventive medicine strategies for zoo birds.

Deep fungal dermatitis in three inland bearded dragons (Pogona vitticeps) caused by the Chrysosporium anamorph of Nannizziopsis vriesii.

The Chrysosporium anamorph of Nannizziopsis vriesii (CANV), a keratinophilic fungus that naturally and experimentally causes severe and often fatal dermatitis in multiple reptile species, was isolated in pure culture from skin samples of three inland bearded dragons (Pogona vitticeps) with deep granulomatous dermatomycosis. The first animal presented with a focal maxillary swelling involving the skin and gingiva. This lizard died while undergoing itraconazole and topical miconazole therapy. The second presented with focally extensive discoloration and thickening of the skin of the ventrum and was euthanized after 10 weeks of itraconazole therapy. A third lizard presented with hyperkeratotic exudative dermatitis on a markedly swollen forelimb. Amputation and itraconazole therapy resulted in a clinical cure. Histopathology of tissue biopsies in all cases demonstrated granulomatous dermatitis with intralesional hyphae morphologically consistent with those produced by the CANV. The second lizard also had granulomatous hepatitis with intralesional hyphae. Evidence in this report suggests that the CANV is the etiologic agent of an emerging condition in captive bearded dragons that has been called 'yellow fungus disease'.