Abstract
Much is unknown regarding the transmission of prion diseases. Hoover's group at Colorado State University investigated the transmission of chronic wasting disease (CWD) in cervids and found that CWD could be detected in white-tailed deer within 12 months after inoculation by saliva or blood from infected animals. Urine and feces, however, did not appear to be efficient routes of transmission. These findings suggest that many tissues from CWD-infected cervids can potentially be infective and that hematogenous spread by insects may play a role in disease transmission in high-density and captive environments. Humans with exposure to cervids that may be CWD-positive should take adequate precautions to avoid exposure to saliva and blood.
Mathiason CK, Powers JG, Dahmes SJ, et al. Infectious prions in the saliva and blood of deer with chronic wasting disease. Science
MDX mice are dystrophin deficient and are a widely used model of Duchenne muscular dystrophy. Typical lesions in these mice include centrally nucleated myofibers, fibrosis, myonecrosis, and inflammatory infiltrate along with decreased muscle strength and decreased treadmill endurance. In this study MDX mice were treated with trichostatin A (TSA), a histone deacetylase inhibitor that increases accessibility of chromatin to transcription factors. TSA-treated MDX mice showed marked increase in myofiber size, increased strength and endurance, markedly less fibrosis, myonecrosis and inflammation, and overall normal muscle architecture. The mechanism for these results appears to be induction of expression of the myostatin antagonist follistatin in the skeletal muscle satellite cells. This work sets the stage for further preclinical studies using deacetylase inhibitors in the treatment of muscular dystrophy and possibly other myopathies.
Minetti GC, Colussi C, Adami R, et al. Functional and morphological recovery of dystrophic muscles in mice treated with deacetylase inhibitors. Nat Med
The p53 protein is one of the most important and widely studied tumor suppressor genes. It is activated in response to DNA damage and oncogenic stress. Activation of p53 in response to DNA damage induces apoptosis and is believed to be critical in preventing tumor development by ridding the body of the damaged cells. Recent work by Efeyan and colleagues demonstrated that the defects in the oncogenic stress pathway may be the more important function. Genetically engineered mice with three functional copies of p53 (p53super) showed additional protection against tumor development compared to wild-type mice with only two copies. However, the protective ability of p53 was abolished in the absence of p19ARF, which is a principle component of the oncogenic stress pathway. Surprisingly, p53super/ARFnull mice developed spontaneous and chemically-induced tumors at the same rate as p53wt/ARFnull mice. The authors conclude that p53 activation by DNA damage has a lesser impact on tumor suppression than previously supposed and that the protective ability of p53 becomes irrelevant in the absence of ARF.
Efeyan A, Garcia-Cao I, Herranz D, Velasco-Miguel S, Serrano M. Policing of oncogenic activity by p53. Nature
Billen and colleagues characterized the distribution of leukocytes in the pharyngeal tonsils of six puppies and eight adult dogs without evidence of respiratory disease. Grossly this tonsillar region was indistinct, but histologically it was more extensive in young dogs than adults. Mast cells were prevalent just beneath the respiratory epithelium. Plasma cells were significantly greater in adults than puppies, with IgA+ cells more numerous than other plasma cell subsets. The majority of lymphoid cells were CD3+, with a greater number of CD4+ than CD8+ cells. Neutrophils were infrequent in both groups but were present in greater numbers in puppies than adults.
Billen F, Peeters D, Dehard S, Day MJ, Clercx C. Distribution of leucocyte subsets in the canine pharyngeal tonsil. J Comp Pathol