Biomarker discovery for ovine paratuberculosis (Johne's disease) by proteomic serum profiling

Paratuberculosis (Johne's disease) is a chronic granulomatous enteritis affecting ruminants and other species. It is caused by Mycobacterium avium subsp. paratuberculosis (MAP). In this study, surface enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI TOF-MS) was used as a platform to identify candidate biomarkers from sheep serum. Multivariate biomarker models which aimed to differentiate sheep with paratuberculosis and vaccinated-exposed sheep from unexposed animals were proposed based on classification and regression tree (CART) and linear discriminant analysis (LDA) algorithms from two array types. The accuracy of classification of sheep into unexposed or exposed groups ranged from 75 to 100% among models. SELDI was used to monitor protein profile changes over time during an experimental infection trial by examining sera collected at 4-, 8- and 13-months post infection. Although three different SELDI instruments were used, nine consistent proteomic features were observed associated with exposure to MAP. Two of the putative serum biomarkers were purified from serum using chromatographic methods and were identified as transthyretin and alpha haemoglobin by tandem mass spectrometry. They belong to highly abundant, acute phase reactants in the serum proteome and have also been discovered as serum biomarkers in human inflammatory conditions and cancer. Their relationship to the pathogenesis of Johne's disease remains to be elucidated.     

Culture of Mycobacterium avium subspecies paratuberculosis (MAP) from blood and extra-intestinal tissues in experimentally infected sheep

Mycobacterium avium subspecies paratuberculosis (MAP) is the causative agent of Johne's disease or paratuberculosis, a chronic enteritis of ruminants, and has been suggested to play a role in Crohn's disease in humans. While Johne's disease is primarily expressed in the gastrointestinal tract, isolation of MAP from extra-intestinal tissues indicates that microbial dissemination via the haematogenous route may occur during the infection. Consequently, the occurrence of mycobacteraemia and dissemination to the liver and hepatic lymph node was investigated in 111 sheep. Disseminated infection was detected in 18 of the 53 sheep that were confirmed to be infected following oral exposure to MAP while the bacterium was isolated from the blood of only 4 of these animals. Disseminated infection was detected more frequently from animals with a positive compared to a negative faecal culture result, multibacillary compared to paucibacillary lesions, and clinical compared to subclinical disease. Detection of MAP in blood by culture was significantly associated with increased time post-exposure and clinical disease, with trends for increased detection in animals with multibacillary lesions and positive faecal culture results. Isolation of MAP from blood was difficult in the early stages of the disease and in paucibacillary animals as the bacteraemia may be intermittent, below the limit of detection or MAP may be present in a dormant non-culturable form. Prolonged incubation periods prior to growth in BACTEC were consistent with inhibition of growth or dormancy in some blood cultures.     

A Magnetic Signature at Io: Initial Report from the Galileo Magnetometer

During the inbound pass of the Galileo spacecraft, the magnetometer acquired 1 minute averaged measurements of the magnetic field along the trajectory as the spacecraft flew by Io. A field decrease, of nearly 40 percent of the background jovian field at closest approach to Io, was recorded. Plasma sources alone appear incapable of generating perturbations as large as those observed and an induced source for the observed moment implies an amount of free iron in the mantle much greater than expected. On the other hand, an intrinsic magnetic field of amplitude consistent with dynamo action at Io would explain the observations. It seems plausible that Io, like Earth and Mercury, is a magnetized solid planet.     

Regulation of Luteal Function and Corpus Luteum Regression in Cows: Hormonal Control, Immune Mechanisms and Intercellular Communication

The main function of the corpus luteum (CL) is production of progesterone (P4). Adequate luteal function to secrete P4 is crucial for determining the physiological duration of the oestrous cycle and for achieving a successful pregnancy. The bovine CL grows very fast and regresses within a few days at luteolysis. Mechanisms controlling development and secretory function of the bovine CL may involve many factors that are produced both within and outside the CL. Some of these regulators seem to be prostaglandins (PGs), oxytocin, growth and adrenergic factors. Moreover, there is evidence that P4 acts within the CL as an autocrine or paracrine regulator. Each of these factors may act on the CL independently or may modify the actions of others. Although uterine PGF_2α is known to be a principal luteolytic factor, its direct action on the CL is mediated by local factors: cytokines, endothelin-1, nitric oxide. The changes in ovarian blood flow have also been suggested to have some role in regulation of CL development, maintenance and regression.