Identification and culture of proliferative cells in abnormal Taenia solium larvae: Role in the development of racemose neurocysticercosis

Racemose neurocysticercosis is an aggressive disease caused by the aberrant expansion of the cyst form of Taenia solium within the subarachnoid spaces of the human brain and spinal cord resulting in a mass effect and chronic inflammation. Although expansion is likely caused by the proliferation and growth of the parasite bladder wall, there is little direct evidence of the mechanisms that underlie these processes. Since the development and growth of cysts in related cestodes involves totipotential germinative cells, we hypothesized that the expansive growth of the racemose larvae is organized and maintained by germinative cells. Here, we identified proliferative cells expressing the serine/threonine-protein kinase plk1 by in situ hybridization. Proliferative cells were present within the bladder wall of racemose form and absent from the homologous tissue surrounding the vesicular form. Cyst proliferation in the related model species Taenia crassiceps (ORF strain) occurs normally by budding from the cyst bladder wall and proliferative cells were concentrated within the growth buds. Cells isolated from bladder wall of racemose larvae were established in primary cell culture and insulin stimulated their proliferation in a dose-dependent manner. These findings indicate that the growth of racemose larvae is likely due to abnormal cell proliferation. The different distribution of proliferative cells in the racemose larvae and their sensitivity to insulin may reflect significant changes at the cellular and molecular levels involved in their tumor-like growth. Parasite cell cultures offer a powerful tool to characterize the nature and formation of the racemose form, understand the developmental biology of T. solium, and to identify new effective drugs for treatment.

Monitoring of Serological Status in Response to PPR Vaccination in the Goat Population of Parbat, Baglung and Myagdi District of Nepal

Peste des Petits ruminants (PPR) is a highly contagious trans-boundary animal disease associated with 100% morbidity and 80-90% mortality in goat herds. The study was carried out to assess the immune status against PPRV in unvaccinated and post vaccinated flock as well as immune response as it relates to age, sex and breed using a homologous tissue culture PPR vaccine produced by National Vaccine Production Laboratory, Kathmandu, Nepal. A total 276 blood samples were randomly collected from different regions of Parbat, Baglung and Myagdi districts with a population of 0.0189 million goats. Out of these, 214 goats were vaccinated one month earlier and 62 were unvaccinated. PPR antibody was detected by using competitive enzyme linked immunosorbent assay (c-ELISA) (ID Screen, PPR competition test kit, IDvet France). Of the unvaccinated goats, 25.8% (16/62) were sero-positive suggesting prior exposure to PPRV. In the vaccinated goats, 75.2% (161/214) were sero-positive and 2.8% (6/214) animals were doubtful, suggesting a significant proportion failed to respond to vaccination. The competition percentage (S/N%±SD) of post-immunization (49.19±32.19) were significantly (p<0.01) lower in comparison to the respective unvaccinated mean titre (75.76±35.51). There is no significant effect of age, sex or breed on the antibody titre value in PPR vaccinated animals. The sero-prevalence of PPR in unvaccinated animals suggested that these flocks are in high susceptibility to PPR outbreak and needs an implementation of control measures to reduce economic losses. Vaccination will increase the proportion of animals with a protective antibody level, however more investigation needs to be done to determine why almost one-quarter of animals failed to seroconvert to vaccination. Further detailed study is needed to find out the risk factors responsible for low prevalence of antibody against PPRV in the immunized flock.

Comparison of the ability of mammalian eEF1A1 and its oncogenic variant eEF1A2 to interact with actin and calmodulin

The question as to why a protein exerts oncogenic properties is answered mainly by well-established ideas that these proteins interfere with cellular signaling pathways. However, the knowledge about structural and functional peculiarities of the oncoproteins causing these effects is far from comprehensive. The 97.5% homologous tissue-specific A1 and A2 isoforms of mammalian translation elongation factor eEF1A represent an interesting model to study a difference between protein variants of a family that differ in oncogenic potential. We propose that the different oncogenic impact of A1 and A2 might be explained by differences in their ability to communicate with their respective cellular partners. Here we probed this hypothesis by studying the interaction of eEF1A with two known partners – calmodulin and actin. Indeed, an inability of the A2 isoform to interact with calmodulin is shown, while calmodulin is capable of binding A1 and interferes with its tRNA-binding and actin-bundling activities in vitro. Both A1 and A2 variants revealed actin-bundling activity; however, the form of bundles formed in the presence of A1 or A2 was distinctly different. Thus, a potential inability of A2 to be controlled by Ca2+-mediated regulatory systems is revealed.

Deformable Image Registration with Inclusion of Autodetected Homologous Tissue Features

A novel deformable registration algorithm is proposed in the application of radiation therapy. The algorithm starts with autodetection of a number of points with distinct tissue features. The feature points are then matched by using the scale invariance features transform (SIFT) method. The associated feature point pairs are served as landmarks for the subsequent thin plate spline (TPS) interpolation. Several registration experiments using both digital phantom and clinical data demonstrate the accuracy and efficiency of the method. For the 3D phantom case, markers with error less than 2 mm are over 85% of total test markers, and it takes only 2-3 minutes for 3D feature points association. The proposed method provides a clinically practical solution and should be valuable for various image-guided radiation therapy (IGRT) applications.