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De Leon L.F.,McGill University | De Leon L.F.,Institute Investigaciones Cientificas Y Servicios Of Alta Tecnologia Aip | De Leon L.F.,Smithsonian Tropical Research Institute | Rolshausen G.,McGill University | And 3 more authors.
Evolutionary Ecology Research | Year: 2012

Background: Empirical and theoretical studies suggest that individual specialization can be an important force in evolutionary diversification. However, few studies of natural populations have explicitly considered the impact of individual specialization on adaptive divergence. Questions: To what extent do individuals within a bimodal Darwin's finch population specialize on different resources? Is this individual specialization likely to enhance adaptive divergence? Field site: El Garrapatero, Santa Cruz Island, Galápagos, Ecuador. Organism: A population of the medium ground finch, Geospiza fortis, showing large - and bimodal - morphological and genetic variation resulting from ecologically based adaptive divergence. Methods: We described the diets of individual G. fortis through feeding observations in the wild. We calculated several indices of individual specialization. We then examined the relationship between individual specialization, adaptive morphological traits (beak and head dimensions), and neutral genetic variation (microsatellites). We also performed a cluster analysis on the basis of individual foraging observations and asked whether the clusters were morphologically and genetically divergent. Results: We found significant levels of individual specialization and expected, but weak, associations between individual diet differences, morphological traits, and neutral genetic variation. The cluster analysis yielded two distinct diet-clusters of individuals that differed in morphological traits but not in neutral genetic markers. In the early stages of adaptive radiation, individual specialization appears to be associated with morphological divergence but not neutral genetic divergence. © 2012 Luis Fernando De León. Source

Spadafora C.,Uniformed Services University of the Health Sciences | Spadafora C.,U.S. Army | Spadafora C.,Institute Investigaciones Cientificas Y Servicios Of Alta Tecnologia Aip | Awandare G.A.,U.S. Army | And 10 more authors.
PLoS Pathogens | Year: 2010

Plasmodium falciparum is a highly lethal malaria parasite of humans. A major portion of its life cycle is dedicated to invading and multiplying inside erythrocytes. The molecular mechanisms of erythrocyte invasion are incompletely understood. P. falciparum depends heavily on sialic acid present on glycophorins to invade erythrocytes. However, a significant proportion of laboratory and field isolates are also able to invade erythrocytes in a sialic acid-independent manner. The identity of the erythrocyte sialic acid-independent receptor has been a mystery for decades. We report here that the complement receptor 1 (CR1) is a sialic acid-independent receptor for the invasion of erythrocytes by P. falciparum. We show that soluble CR1 (sCR1) as well as polyclonal and monoclonal antibodies against CR1 inhibit sialic acid-independent invasion in a variety of laboratory strains and wild isolates, and that merozoites interact directly with CR1 on the erythrocyte surface and with sCR1- coated microspheres. Also, the invasion of neuraminidase-treated erythrocytes correlates with the level of CR1 expression. Finally, both sialic acid-independent and dependent strains invade CR1 transgenic mouse erythrocytes preferentially over wild-type erythrocytes but invasion by the latter is more sensitive to neuraminidase. These results suggest that both sialic acid-dependent and independent strains interact with CR1 in the normal red cell during the invasion process. However, only sialic acid-independent strains can do so without the presence of glycophorin sialic acid. Our results close a longstanding and important gap in the understanding of the mechanism of erythrocyte invasion by P. falciparum that will eventually make possible the development of an effective blood stage vaccine. Source

Augusto Martinez A.,Gorgas Memorial Institute for Health Studies | Augusto Martinez A.,Acharya Nagarjuna University | Augusto Martinez A.,Institute Investigaciones Cientificas Y Servicios Of Alta Tecnologia Aip | Zaldivar Y.,Gorgas Memorial Institute for Health Studies | And 8 more authors.
Memorias do Instituto Oswaldo Cruz | Year: 2013

Despite the effectiveness of current hepatitis B virus (HBV) vaccines, it is estimated that 350 million individuals suffer from chronic HBV infection and more than 50% of these affected individuals live on the Asian continent. Panama is a country with a great diversity of foreign groups; the Chinese community is a large example of this phenomenon. There is an urgent need to perform studies that evaluate the prevalence and the genetic diversity of HBV in this community. This study aimed to evaluate the prevalence of HBV and its genotypes and mutant variants in the Chinese population residing in Panama. In total, 320 subjects were enrolled in the study. Forty-two subjects (13.1%) were positive for HBsAg and HBV-DNA from 18 subjects revealed the presence of genotypes B2 and C1. Secondary mutations associated with drug resistance at positions rtV207L and rtN239T of the reverse transcriptase gene were identified. Additionally, the mutation pair A1762T/G1764A was found in three samples and the mutation G1896A was detected in an HBeAg-negative subject. In conclusion, to our knowledge, this is the first study to report high HBV prevalence rates in resident ethnic Chinese in Central America and the presence of genotypes B2 and C1 in this region. Source

Romanha A.J.,Integrado de Doenca de Chagas Fiocruz | Romanha A.J.,Instituto Rene Rachou Fiocruz | de Castro S.L.,Integrado de Doenca de Chagas Fiocruz | de Castro S.L.,Instituto Oswaldo Cruz Fiocruz | And 30 more authors.
Memorias do Instituto Oswaldo Cruz | Year: 2010

Chagas disease, a neglected illness, affects nearly 12-14 million people in endemic areas of Latin America. Although the occurrence of acute cases sharply has declined due to Southern Cone Initiative efforts to control vector transmission, there still remain serious challenges, including the maintenance of sustainable public policies for Chagas disease control and the urgent need for better drugs to treat chagasic patients. Since the introduction of benznidazole and nifurtimox approximately 40 years ago, many natural and synthetic compounds have been assayed against Trypanosoma cruzi, yet only a few compounds have advanced to clinical trials. This reflects, at least in part, the lack of consensus regarding appropriate in vitro and in vivo screening protocols as well as the lack of biomarkers for treating parasitaemia. The development of more effective drugs requires (i) the identification and validation of parasite targets, (ii) compounds to be screened against the targets or the whole parasite and (iii) a panel of minimum standardised procedures to advance leading compounds to clinical trials. This third aim was the topic of the workshop entitled Experimental Models in Drug Screening and Development for Chagas Disease, held in Rio de Janeiro, Brazil, on the 25th and 26th of November 2008 by the Fiocruz Program for Research and Technological Development on Chagas Disease and Drugs for Neglected Diseases Initiative. During the meeting, the minimum steps, requirements and decision gates for the determination of the efficacy of novel drugs for T. cruzi control were evaluated by interdisciplinary experts and an in vitro and in vivo flowchart was designed to serve as a general and standardised protocol for screening potential drugs for the treatment of Chagas disease. Source

Spadafora C.,U.S. Army | Spadafora C.,Institute Investigaciones Cientificas Y Servicios Of Alta Tecnologia Aip | Gerena L.,U.S. Army | Kopydlowski K.M.,U.S. Army
Malaria Journal | Year: 2011

Background: Percoll gradient centrifugation is often used for synchronization, enrichment, or isolation of a particular stage of Plasmodium falciparum. However, Percoll, a hyperosmotic agent, may have harmful effects on the parasites. Magnetic bead column (MBC) separation has been used as an alternative. This is a report of a head-to-head comparison of the in vitro invasive capabilities of parasites isolated by either of the two methods. Methods. The P. falciparum laboratory strain isolate 7G8 was grown in vitro using standard procedures and synchronized using 5% sorbitol. On separate days when the schizont parasitaemia was 1%, the culture was split and half was processed by Percoll gradient centrifugation and the other half by magnetic bead column separation. Both processed parasites were placed back in culture and allowed to invade new uninfected erythrocytes. Results: In 10 paired assays, the mean efficiency of invasion of 7G8 parasites treated by Percoll gradient centrifugation was 35.8% that of those treated by magnetic bead column separation (95% CI, p = 0.00067) A paired t test with two tails was used for these comparisons. Conclusions: In this comparison, magnetic bead column separation of 7G8 schizonts resulted in higher viability and efficiency of invasion than utilizing Percoll gradient centrifugation. © 2011 Spadafora et al; licensee BioMed Central Ltd. Source

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