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Int J Biol Macromol,
2015]
Lymphatic filariasis (LF), a morbid vector-borne parasitic infection affects millions in tropical areas. Complete eradication can only be achieved by the development of a potent vaccine. Among the various filarial antigens that have been characterized, antigens Brugia malayi thioredoxin (TRX) and abundant larval transcript (ALT) have produced recognizable level of protection in Jirds, thereby evidenced to be good vaccine candidates. In this study an attempt was made to enhance their immunoprophylactic activity by encapsulating them in natural polysaccharide chitosan forming nanospheres (CN). High encapsulation efficiency for TRX (93%) in CN (TCN) and ALT-2 (90%) in CN (ACN) was achieved. Morphological studies confirmed the spherical and uniform distribution of nanospheres to be 220 nm. The electrostatic interaction between chitosan and the antigens were confirmed using differential scanning calorimetry and FT-IR. The study revealed the immunostimulatory property of chitosan providing enhanced level of proliferation for encapsulated antigens in peripheral blood mononuclear cells from endemic normal personals, at low concentration (TCN mean stimulation index (SI)=4.23+/-0.15 and ACN (SI)=4.05+/-0.33) compared to stimulation obtained by antigens alone. Hence, our study demonstrated that natural macromolecule derived CN can be used as efficacious immunostimulatory vaccine carter for LF thereby diminishing pathological sequel.
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J Cell Biol,
2007]
Microtubules deliver positional signals and are required for establishing polarity in many different organisms and cell types. In Caenorhabditis elegans embryos, posterior polarity is induced by an unknown centrosome-dependent signal. Whether microtubules are involved in this signaling process has been the subject of controversy. Although early studies supported such an involvement (O''Connell, K.F., K.N. Maxwell, and J.G. White. 2000. Dev. Biol. 222:55-70; Wallenfang, M.R., and G. Seydoux. 2000. Nature. 408:89-92; Hamill, D.R., A.F. Severson, J.C. Carter, and B. Bowerman. 2002. Dev. Cell. 3:673-684), recent work involving RNA interference knockdown of tubulin led to the conclusion that centrosomes induce polarity independently of microtubules (Cowan, C.R., and A.A. Hyman. 2004. Nature. 431:92-96; Sonneville, R., and P. Gonczy. 2004. Development. 131: 3527-3543). In this study, we investigate the consequences of tubulin knockdown on polarity signaling. We find that tubulin depletion delays polarity induction relative to wild type and that polarity only occurs when a small, late-growing microtubule aster is visible at the centrosome. We also show that the process of a normal meiosis produces a microtubule-dependent polarity signal and that the relative levels of anterior and posterior PAR (partitioning defective) polarity proteins influence the response to polarity signaling. Our results support a role for microtubules in the induction of embryonic polarity in C. elegans.
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Ann Trop Med Parasitol,
2008]
Human onchocerciasis (river blindness) occurs in 13 foci distributed among six countries in Latin America (Brazil, Colombia, Ecuador, Guatemala, Mexico and Venezuela), where about 500,000 people are considered at risk. An effort to eliminate the disease from the region was launched in response to a specific resolution adopted by the PanAmerican Health Organization (PAHO) in 1991: to eliminate onchocerciasis from the region, as a public-health problem, by 2007. The effort took advantage of the donation of the drug Mectizan (ivermectin) by Merck & Co., Inc. In 1992, the Onchocerciasis Elimination Program for the Americas (OEPA) was launched, with its headquarters in Guatemala, to act as a technical and co-ordinating body of a multinational, multi-agency coalition that includes the endemic countries, PAHO, The Carter Center, Lions Clubs, the United States Centers for Disease Control and Prevention, The Bill and Melinda Gates Foundation, Merck & Co., Inc., and other partners. This public-private partnership facilitated the establishment of programmes for the semi-annual mass administration of Mectizan in the six countries with onchocerciasis. The aims were to (1) provide sustained treatments, with coverage reaching at least 85% of those eligible to receive the drug (in the 1845 endemic communities that are distributed within the 13 regional foci); (2) eliminate new morbidity caused by Onchocerca volvulus infection by 2007; and (3) eliminate transmission of the parasite wherever feasible. Significant progress has already been made in all six countries, each of which has active programmes with treatment coverages exceeding the target of 85%. The progress is being documented in accordance with certification guidelines for onchocerciasis elimination established by the World Health Organization. No new cases of onchocercal blindness are being reported in the region, and ocular disease attributable to O. volvulus has been eliminated from nine of the 13 foci. Treatment is no longer needed in Santa Rosa, Guatemala, where transmission has been eliminated, and will be halted in at least three other foci in 2008, as they confirm the interruption of transmission. Treatment efforts should now be concentrated on the five foci where significant transmission remains: Central (Guatemala), Amazonas/Roraima (Brazil), North-central (Venezuela), North-east (Venezuela) and South (Venezuela). Based upon the experience gained, the well-established operations and the success achieved so far, it seems reasonable to estimate that onchocerciasis could be eliminated from most of the remaining foci in the Americas by 2012. The protocol, criteria and deadline for stopping all onchocerciasis treatment in the region should soon be addressed by OEPA's Program Co-ordinating Committee (PCC), in co-ordination with the PAHO.