563 research outputs found
Preclinical assessment of the receptor-binding domain of Plasmodium vivax duffy-binding protein as a vaccine candidate in rhesus macaques
The receptor-binding domain of Plasmodium vivax Duffy-binding protein, region II (PvRII), is an attractive candidate for a vaccine against P. vivax malaria. Here, we have studied the safety and immunogenicity of recombinant PvRII in Macaca mulatta (rhesus monkeys). Recombinant PvRII with a C-terminal 6-histidine tag was expressed in E. coli, recovered from inclusion bodies, refolded into its functional conformation, purified to homogeneity and formulated with three adjuvants, namely, Alhydrogel, Montanide ISA 720 and the GSK proprietary Adjuvant System AS02A for use in immunogenicity studies. All the PvRII vaccine formulations tested were safe and highly immunogenic. The overall magnitude of the antibody response was significantly higher for both Montanide ISA 720 and AS02A formulations in comparison with Alhydrogel. Furthermore, there was a significant correlation between antibody recognition titers by ELISA and binding inhibition titers in in vitro binding assays. The PvRII vaccine formulations also induced IFN-γ recall responses that were identified using ex vivo ELISPOT assays. These results provide support for further clinical development of a vaccine for P. vivax malaria based on recombinant PvRII
Magnetic manipulation of superparamagnetic colloids in droplet-based optical devices
Magnetically assembled superparamagnetic colloids have been exploited as
fluid mixers, swimmers and delivery systems in several microscale applications.
The encapsulation of such colloids in droplets may open new opportunities to
build magnetically controlled displays and optical components. Here, we study
the assembly of superparamagnetic colloids inside droplets under rotating
magnetic fields and exploit this phenomenon to create functional optical
devices. Colloids are encapsulated in monodisperse droplets produced by
microfluidics and magnetically assembled into dynamic two-dimensional clusters.
Using an optical microscope equipped with a magnetic control setup, we
investigate the effect of the magnetic field strength and rotational frequency
on the size, stability and dynamics of 2D colloidal clusters inside droplets.
Our results show that cluster size and stability depend on the magnetic forces
acting on the structure under the externally imposed field. By rotating the
cluster in specific orientations, we illustrate how magnetic fields can be used
to control the effective refractive index and the transmission of light through
the colloid-laden droplets, thus demonstrating the potential of the
encapsulated colloids in optical applications
Measurement of the 18Ne(a,p_0)21Na reaction cross section in the burning energy region for X-ray bursts
The 18Ne(a,p)21Na reaction provides one of the main HCNO-breakout routes into
the rp-process in X-ray bursts. The 18Ne(a,p_0)21Na reaction cross section has
been determined for the first time in the Gamow energy region for peak
temperatures T=2GK by measuring its time-reversal reaction 21Na(p,a)18Ne in
inverse kinematics. The astrophysical rate for ground-state to ground-state
transitions was found to be a factor of 2 lower than Hauser-Feshbach
theoretical predictions. Our reduced rate will affect the physical conditions
under which breakout from the HCNO cycles occurs via the 18Ne(a,p)21Na
reaction.Comment: 5 pages, 3 figures, accepted for publication on Physical Review
Letter
Merozoite surface protein-3α is a reliable marker for population genetic analysis of Plasmodium vivax
BACKGROUND: The knowledge on population structure of the parasite isolates has contributed greatly to understanding the dynamics of the disease transmission for designing and evaluating malaria vaccines as well as for drug applications. msp-1 and msp-3α genes have been used as a genetic marker in population studies of Plasmodium vivax isolates. In this study, msp-3α was compared and assessed with msp-1 marker in order to find whether msp-3α is a reliable genetic marker for P. vivax population studies. METHODS: This comparative study was designed and carried out as the first assessment of diversity in Pvmsp-3α gene by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in the 50 northern and 94 southern P. vivax isolates from Iran, which had been analysed before for msp-1 gene. RESULTS: Three allele size as, Type A (1.8 kb), Type B (1.5 kb) and Type C (1.2 kb) have been detected among both northern and southern isolates based on PCR results. Type C (70%) and Type A (68.7%) were the predominant fragments among northern and southern parasites, respectively. 99 distinct Pvmsp-3α fragments defined by the size were detected in the 94 southern samples by PCR analysis. However, no mixed genotype infections have been detected among northern isolates. Based on restriction pattern from digestion with Hha I and Alu I 12 and 49 distinct allelic variants have been detected among 50 northern and 94 southern isolates. However, based on msp-1 gene, 30 distinct variants identified in all 146-sequenced Iranian P. vivax isolate. CONCLUSION: The results suggested that PCR-RFLP on msp-3α gene is an adequate, applicable and easily used technique for molecular epidemiology studies of P. vivax isolates without the need for further sequencing analysis
Comparison of the human immune responses to recombinant proteins representing three distinct surface proteins of Plasmodium vivax merozoites
Universidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM) Departamento de Microbiologia, Imunologia e ParasitologiaUniversidade Federal do Pará Departamento de PatologiaCenters for Disease Control and Prevention Division of Parasitic DiseasesInstituto Evandro ChagasUniversidade Federal de Minas Gerais Departamento de ParasitologiaUNIFESP, EPM, Depto. de Microbiologia, Imunologia e ParasitologiaSciEL
Measurement of two-halo neutron transfer reaction p(Li,Li)t at 3 MeV
The p(\nuc{11}{Li},\nuc{9}{Li})t reaction has been studied for the first time
at an incident energy of 3 MeV delivered by the new ISAC-2 facility at
TRIUMF. An active target detector MAYA, build at GANIL, was used for the
measurement. The differential cross sectionshave been determined for
transitions to the \nuc{9}{Li} ground andthe first excited states in a wide
range of scattering angles. Multistep transfer calculations using different
\nuc{11}{Li} model wave functions, shows that wave functions with strong
correlations between the halo neutrons are the most successful in reproducing
the observation.Comment: 6 pages, 3 figures, submitted to Physical Review Letter
Disease progression in Plasmodium knowlesi malaria is linked to variation in invasion gene family members.
Emerging pathogens undermine initiatives to control the global health impact of infectious diseases. Zoonotic malaria is no exception. Plasmodium knowlesi, a malaria parasite of Southeast Asian macaques, has entered the human population. P. knowlesi, like Plasmodium falciparum, can reach high parasitaemia in human infections, and the World Health Organization guidelines for severe malaria list hyperparasitaemia among the measures of severe malaria in both infections. Not all patients with P. knowlesi infections develop hyperparasitaemia, and it is important to determine why. Between isolate variability in erythrocyte invasion, efficiency seems key. Here we investigate the idea that particular alleles of two P. knowlesi erythrocyte invasion genes, P. knowlesi normocyte binding protein Pknbpxa and Pknbpxb, influence parasitaemia and human disease progression. Pknbpxa and Pknbpxb reference DNA sequences were generated from five geographically and temporally distinct P. knowlesi patient isolates. Polymorphic regions of each gene (approximately 800 bp) were identified by haplotyping 147 patient isolates at each locus. Parasitaemia in the study cohort was associated with markers of disease severity including liver and renal dysfunction, haemoglobin, platelets and lactate, (r = ≥ 0.34, p =  <0.0001 for all). Seventy-five and 51 Pknbpxa and Pknbpxb haplotypes were resolved in 138 (94%) and 134 (92%) patient isolates respectively. The haplotypes formed twelve Pknbpxa and two Pknbpxb allelic groups. Patients infected with parasites with particular Pknbpxa and Pknbpxb alleles within the groups had significantly higher parasitaemia and other markers of disease severity. Our study strongly suggests that P. knowlesi invasion gene variants contribute to parasite virulence. We focused on two invasion genes, and we anticipate that additional virulent loci will be identified in pathogen genome-wide studies. The multiple sustained entries of this diverse pathogen into the human population must give cause for concern to malaria elimination strategists in the Southeast Asian region
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