BackgroundThe R2 repeat region of GLURP has been reported as a good genetic marker for Plasmodium falciparum genotyping. Proper knowledge of the extent and nature of P. falciparum genetic diversity using highly immunogenic R2 repeat region in malaria-endemic areas is a crucial element to understand various aspects related to immunity acquisition and disease pathogenesis.MethodsPopulation diversity of P. falciparum GLURP and amino acid sequence repeats in GLURP R2 region was studied in malaria-endemic Assam state, northeast India and compared at an interval of five years during 2005 (Group-A) and 2011 (Group-B).ResultsOf the 66 samples, a total of 55 samples showed positive PCR bands for GLURP R2 region and altogether ten types of alleles with size ranging from 501 bp to 1,050 bp (50 bp bin) were observed and coded as genotypes I-X. In Group-A (n = 29), 24 samples were found infected with single, four with double and one with triple P. falciparum genotype, while in Group-B (n = 26), single genotype was found in 23 samples, double in two samples and triple in one sample. Genotype IV showed significant increase (p = 0.002) during 2011 (Group-B). Genotypes I to V were more common in Group-B (62%), however genotypes VI to X were more frequently distributed in Group-A. The expected heterozygosity was found slightly higher in Group-A (HE = 0.87) than Group-B (HE = 0.85), whereas multiplicity of infection (MOI) in Group-A (MOI = 1.21 ± 0.49) and Group-B (MOI = 1.12 ± 0.43) did not display significant variation. The amino acid repeat sequence unit (AAU) DKNEKGQHEIVEVEEILPE (called ‘a’) was more frequent in the well-conserved part of R2 repeat region.ConclusionThe present study is the first extensive study in India which has generated substantial data for understanding the type and distribution of naturally evolved genetic polymorphism at amino acid sequence level in GLURP R2 repeat region in P. falciparum. There was decrease in the PCR amplicon size as well as the number of AAU [amino acid repeat unit] in Group-B displaying the bottleneck effect. The present study described a new type of AAU ‘d’ which varied from the other previous known AAUs.Electronic supplementary materialThe online version of this article (doi:10.1186/1475-2875-13-450) contains supplementary material, which is available to authorized users.
Iron overload causes progressive and sometimes irreversible damage due to accelerated production of reactive oxygen species. Desferrioxamine (DFO), a siderophore, has been used clinically to remove excess iron. However, the applications of DFO are limited because of its inability to access intracellular labile iron. Cell penetrating peptides (CPPs) have become an efficient delivery vector for the enhanced internalization of drugs into the cytosol. We describe, herein, an efficient method for covalently conjugating DFO to the CPPs TAT(47-57) and Penetratin. Both conjugates suppressed the redox activity of labile plasma iron in buffered solutions and in iron-overloaded sera. Enhanced access to intracellular labile iron compared to the parent siderophore was achieved in HeLa and RBE4 (a model of blood-brain-barrier) cell lines. Iron complexes of both conjugates also had better permeability in both cell models. DFO antioxidant and iron binding properties were preserved and its bioavailability was increased upon CPP conjugation, which opens new therapeutic possibilities for neurodegenerative processes associated with brain iron overload.
The present paper reports the photophysical aspects of a very interesting and unique host-guest interaction between fullerene and phthalocyanines, viz., free base phthalocyanine (H2-Pc) and zinc-phthalocyanine (Zn-Pc), in toluene medium. Ground state electronic interaction between these two supramolecules has been evidenced from the observation of well-defined charge transfer (CT) absorption bands in the visible region. Vertical ionization potentials of the phthalocyanines have been determined utilizing CT transition energy. Magnitude of degrees of CT reveals that, in the ground state, 2-4% CT takes place. Binding constants (K) for the fullerene/phthalocyanine complexes were determined from the fluorescence quenching experiment. Large K values in the ranges approximately 4.7 x 10(4) to 7.3 x 10(4) and 2.3 x 10(4) to 2.5 x 10(4) dm(3) x mol(-1) were obtained for the 1:1 fullerene complexes of Zn and H 2-Pc, respectively. Values of K suggest that both H 2- and Zn-Pc could not serve as an efficient discriminators between C60 and C70. Theoretical calculations as well as (13)C NMR studies establish that the orientation of C 70 toward phthalocyanine is favored in end-on orientation, which proves that interaction between fullerenes and phthalocyanines were governed by the electrostatic mechanism rather than dispersive forces associated with pi-pi interaction.
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