Crystal structure of the malaria vaccine candidate apical membrane antigen 1

Apical membrane antigen 1 from Plasmodium is a leading malaria vaccine candidate. The protein is essential for host-cell invasion, but its molecular function is unknown. The crystal structure of the three domains comprising the ectoplasmic region of the antigen from P. vivax, solved at 1.8 angstrom resolution, shows that domains I and II belong to the PAN motif, which defines a superfamily of protein folds implicated in receptor binding. We also mapped the epitope of an invasion-inhibitory monoclonal antibody specific for the P. falciparum ortholog and modeled this to the structure. The location of the epitope and current knowledge on structure-function correlations for PAN domains together suggest a receptor-binding role during invasion in which domain II plays a critical part. These results are likely to aid vaccine and drug design.     

Isotype- and subclass-specific responses to infection and reinfection with parainfluenza-3 virus: comparison of the diagnostic potential of ELISAs detecting seroconversion and specific IgM and IgA.

Isotype- and subclass-specific indirect enzyme-linked immunosorbent assays were developed to detect parainfluenza-3 virus-specific IgG1, IgG2, IgM, and IgA responses. Sera were treated with protein G-agarose prior to testing for specific IgM and IgA to eliminate the possibility of false-positive results due to IgM-rheumatoid factor and to remove interisotypic competition due to specific IgG. IgM and IgA absorbance values were expressed as a percentage of the absorbance values of positive reference sera included on each plate (S/P%), and respective positive/negative threshold values of 15.0% and 28.0% were determined. The mean interval between experimental infection of 3 calves and initial detection of specific IgG1 and IgG2 responses was 8.0 and 9.3 days respectively, rising rapidly to an initial plateau 13.7 and 11.0 days postinfection (dpi). Reinfection of these calves at 30 dpi resulted in further rapid increases, with higher plateau values reached 13.0 (IgG1) and 13.7 (IgG2) days later. The mean interval between infection and the first positive IgM and IgA responses was 6.7 and 12.3 days, respectively. IgM S/P% values peaked at 13.0 dpi, with all 3 calves showing a secondary anamnestic response to reinfection, peaking 4.7 days later. The IgA response to initial infection was weak, with only 2 calves showing an obvious peak response at 15.0 dpi. A strong anamnestic IgA response to reinfection occurred in 2 calves, with a peak response 9.5 days later. Apparent biphasic and triphasic IgM and IgA responses were evident in some calves. Acute and convalescent serum samples from 80 calves involved in 17 outbreaks of respiratory disease were tested for specific IgM and IgA. Positive IgM results were detected in 15 outbreaks, with 71 sera from 44 calves testing positive. Although IgA-positive results were detected in the same 15 outbreaks, only 42 sera from 31 calves were positive. In a previous study, seroconversion was detected in 21 of these calves from 10 outbreaks. Thus the diagnostic potential of the assays was in the order IgM > IgA > seroconversion. The correlations between IgM and IgA, IgM and seroconversion, and IgA and seroconversion results for each calf were 73.8%, 58.8% and 62.5%, respectively.     

Reproductive characteristics of the fishery important temperate demersal berycid Centroberyx gerrardi indicate greater reproductive output in regions of upwelling

The reproductive biology of Centroberyx gerrardi (Günther) was investigated across ~2,000 km of its southern Australian distribution, encompassing different jurisdictions and varying environmental features. Greater gonad mass and prevalence of spawning fish, along with lower ratios of lengths at maturity:maximum lengths and ages at maturity:maximum ages, were identified at the western‐most (Capes) and eastern‐most (Great Australian Bight; GAB) regions. Across the study region, spawning peaks in summer/autumn, when water temperatures are warmest. Regional differences in potential “reproductive output,” while not consistent with the eastward decline in mean monthly water temperature, may instead be related to summer upwelling in the Capes and GAB, driving greater oceanic productivity prior to peak spawning, supporting larval survival. In autumn, the prevailing southward and eastward flowing, downwelling Leeuwin Current (LC) strengthens, providing a dispersal mechanism along the west and south Australian coasts, but limiting upwelling effects. Predicted changes in environmental conditions and their potential impacts on C. gerrardi are discussed, in particular how these factors may affect recruitment to stocks and fisheries, requiring a better understanding of source‐sink relationships for this species. As environmental changes occur, management strategies to sustain fish resources must adapt to spatially variable and changing reproductive output and be collaborative across jurisdictions.     

Evaluation of the recognition of Theileria parva vaccine candidate antigens by cytotoxic T lymphocytes from Zebu cattle

East Coast fever (ECF) is a highly fatal lymphoproliferative disease of cattle caused by Theileria parva, a tick-borne intracellular apicomplexan parasite. Parasite antigens that are targets of protective cytotoxic T lymphocyte (CTL) responses are required to formulate a sub-unit vaccine against ECF. A number of CTL target antigens have recently been identified and initial evaluation has shown their vaccine potential. This study aimed to evaluate whether these antigens were recognised by CTL obtained from six genetically diverse Zebu cattle immunized with a cocktail of T. parva stocks. T. parva Muguga specific polyclonal CD8(+) CTL lines were generated and confirmed to specifically lyse autologous infected cells. CTL recognition of autologous skin fibroblasts (iSF) transduced with recombinant modified vaccinia virus Ankara strain (MVA) expressing previously identified T. parva Muguga vaccine candidate antigens was evaluated using an IFN-gamma ELISpot assay. CTL lines from one of the four calves, BY120, responded specifically to cells infected with MVA expressing the antigen Tp2 and synthetic peptides were employed to map a new CTL epitope on this antigen. Immunoscreening of the T. parva genome with these CTL lines should identify novel antigens that will constitute valuable additions to the vaccine candidates currently being evaluated.     

Cervical intervertebral disc protrusion in two horses

Two horses with ataxia of all four limbs were found to have cervical intervertebral disc protrusion. Severe pelvic limb ataxia, proprioceptive deficits and spasticity were present in both horses with similar but less severe signs in the thoracic limbs. Cerebrospinal fluid analysis was within normal limits. Metrizamide myelography allowed definitive diagnosis in one case when a compression of the spinal cord was demonstrated at the level of the second intervertebral space. In the second case, an intervertebral disc protrusion between cervical vertebrae 6 and 7 was found at necropsy. Fiber degeneration with poor myelin staining characterized the spinal cords histologically.     

Experimental hybridization in certain diploid mexican solanum species

S. bulbocastanum is highly interfertile with S. cardiophyllum. Through the F₁ to F₅ little breakdown due to sterility or lack of plant vigour occurred. F₁ plants of a 5-species hybrid involving S. pinnatisectum, S. trifidum, S. jamesii, S. bulbocastanum, and S. cardiophyllum could also be intercrossed. One-way compatibility was frequently expressed in progenies of these interspecific crosses. It appears to be cytoplasmically controlled, although nuclear factors may be present which interact with cytoplasmic factors. The group of Mexican diploid potatoes represented by these species is potentially interbreeding and shows evidence of introgression throughout its range in central and Western Mexico.Contribution No. 169, Canada Department of Agriculture Research Station, Fredericton, New Brunswick, Canada