We previously identified by immunoscreening Trypanosoma cruzi cDNA libraries a group of proteins containing long stretches of tandem repeats. The goal of the current project was to gain insight into ...the functions of these proteins through ultrastructural analyses consisting of western blotting and electron microscopic localization studies. By comparing western blots of total parasite lysate and different fractions of T. cruzi, we found that 3 of the repetitive antigens are exclusively associated with the parasite membrane, or cytoskeleton, or both. One of the 4 repetitive antigens studied has some association with the membrane or cytoskeleton but also appears to be free in the cytosol. In immunoelectron microscopic studies, the 4 repetitive antigens were detected in different intracellular locations. One of the proteins is located between the flagellum and parasite body, the second has a nuclear distribution, the third is associated with the cell membrane, and the fourth is dispersed throughout the cytoskeletal network. These findings suggest that despite the general structural similarities of these repetitive proteins, they may serve different cellular functions.
The potential use of the Trypanosoma cruzi metacyclic trypomastigote
(MT) stage-specific molecule glycoprotein-82 (gp82) as a vaccine target
has not been fully explored. We show that the opsonization ...of T. cruzi
MT with gp82-specific antibody prior to mucosal challenge significantly
reduces parasite infectivity. In addition, we investigated the immune
responses as well as the systemic and mucosal protective immunity
induced by intranasal CpG-adjuvanted gp82 vaccination. Spleen cells
from mice immunized with CpG-gp82 proliferated and secreted IFN-γ
in a dose-dependent manner in response to in vitro stimulation with
gp82 and parasite lysate. More importantly, these CpG-gp82-immunized
mice were significantly protected from a biologically relevant oral
parasite challenge.
Generation of novel Chagas vaccines Eickhoff, Christopher S.; Ardito, Matthew; Gustafson, Eric ...
Proceedings of the 2nd ACM Conference on Bioinformatics, Computational Biology and Biomedicine,
08/2011
Conference Proceeding
Chagas disease, caused by persistent chronic infection with the tropical parasite Trypanosoma cruzi, remains a severe cause of morbidity and mortality in the South American poor population. There are ...no Chagas vaccines for human use available nor in human clinical vaccine trials. We have previously shown that T cells alone provide protection to normally susceptible BALB/c mice against lethal systemic parasite challenge. The availability of 'humanized' mice (i.e., HLA DR1/A2 dual transgenic mice) allows us to perform similar studies eliciting data more relevant to human Chagas vaccine development. The goals of our evolving studies are to:
1) identify sequences predicted to bind multiple HLA alleles within a) the highly conserved functional (enzymatically active) trans-sialidase (TS) gene family members, b) the larger subset of non-functional TS genes, and c) the total gene subset expressed during human infection,
2) verify that predicted epitopes are presented by MHC during human T. cruzi infection,
3) prepare several DNA vaccines encoding multiple class I and class II parasite epitopes, and
4) perform immunization/challenge experiments in HLA-DR1/A2 dual transgenic mice to determine whether these novel T cell-driven vaccines induce immunity protective against acute lethal challenges as well as against chronic inflammation and disease.
The semiconducting properties of a bithiophene-naphthalene diimide copolymer (PNDIT2) prepared by Ni-catalyzed chain-growth polycondensation (P1) and commercially available N2200 synthesized by ...Pd-catalyzed step-growth polycondensation were compared. Both polymers show similar electron mobility of similar0.2 cm2 V−1 s−1, as measured in top-gate OFETs with Au source/drain electrodes. It is noteworthy that the new synthesis has several technological advantages compared to traditional Stille polycondensation, as it proceeds rapidly at room temperature and does not involve toxic tin-based monomers. Furthermore, a step forward to fully printed polymeric devices was achieved. To this end, transistors with PEDOT:PSS source/drain electrodes were fabricated on plastic foils by means of mass printing technologies in a roll-to-roll printing press. Surface treatment of the printed electrodes with PEIE, which reduces the work function of PEDOT:PSS, was essential to lower the threshold voltage and achieve high electron mobility. Fully polymeric P1 and N2200-based OFETs achieved average linear and saturation FET mobilities of >0.08 cm2 V−1 s−1. Hence, the performance of n-type, plastic OFET devices prepared in ambient laboratory conditions approaches those achieved by more sophisticated and expensive technologies, utilizing gold electrodes and time/energy consuming thermal annealing and lithographic steps.
Dieser Beitrag ist aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.
The semiconducting properties of a bithiophene-naphthalene diimide copolymer (PNDIT2) prepared by Ni-catalyzed chain-growth polycondensation (P1) and commercially available N2200 synthesized by ...Pd-catalyzed step-growth polycondensation were compared. Both polymers show similar electron mobility of similar0.2 cm2 V−1 s−1, as measured in top-gate OFETs with Au source/drain electrodes. It is noteworthy that the new synthesis has several technological advantages compared to traditional Stille polycondensation, as it proceeds rapidly at room temperature and does not involve toxic tin-based monomers. Furthermore, a step forward to fully printed polymeric devices was achieved. To this end, transistors with PEDOT:PSS source/drain electrodes were fabricated on plastic foils by means of mass printing technologies in a roll-to-roll printing press. Surface treatment of the printed electrodes with PEIE, which reduces the work function of PEDOT:PSS, was essential to lower the threshold voltage and achieve high electron mobility. Fully polymeric P1 and N2200-based OFETs achieved average linear and saturation FET mobilities of >0.08 cm2 V−1 s−1. Hence, the performance of n-type, plastic OFET devices prepared in ambient laboratory conditions approaches those achieved by more sophisticated and expensive technologies, utilizing gold electrodes and time/energy consuming thermal annealing and lithographic steps.
Dieser Beitrag ist aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.