Plasmodium falciparum antigenic diversity: Evidence of clonal population structure

Plasmodium falciparum, the agent of malignant malaria, is one of mankind’s most severe scourges. Efforts to develop preventive vaccines or remedial drugs are handicapped by the parasite’s rapid evolution of drug resistance and protective antigens. We examine 25 DNA sequences of the gene coding for the highly polymorphic antigenic circumsporozoite protein. We observe total absence of silent nucleotide variation in the two nonrepeated regions of the gene. We propose that this absence reflects a recent origin (within several thousand years) of the world populations of P. falciparum from a single individual; the amino acid polymorphisms observed in these nonrepeat regions would result from strong natural selection. Analysis of these polymorphisms indicates that: (i) the incidence of recombination events does not increase with nucleotide distance; (ii) the strength of linkage disequilibrium between nucleotides is also independent of distance; and (iii) haplotypes in the two nonrepeat regions are correlated with one another, but not with the central repeat region they span. We propose two hypotheses: (i) variation in the highly polymorphic central repeat region arises by mitotic intragenic recombination, and (ii) the population structure of P. falciparum is clonal—a state of affairs that persists in spite of the necessary stage of physiological sexuality that the parasite must sustain in the mosquito vector to complete its life cycle.     

Molecular structure of the octamer d(G-G-C-C-G-G-C-C): modified A-DNA.

The deoxynucleotide fragment d(GpGpCpCpGpGpCpC) was synthesized and crystallized, and its three-dimensional structure was determined by x-ray diffraction techniques to a resolution of 2.25 A. The molecule forms a right-handed double helix in which the two base pairs at either end of the molecule are in the conventional A-DNA conformation, while the central four base pairs have a modified form in which alternate residues have sugar conformations that are closer to those in B-DNA than in A-DNA. The molecules have an intermolecular contact in which the planar terminal guanine . cytosine base pair lies on the flat minor groove surface of the A-DNA helix.     

Dynamic photoacoustic imaging of neurovascular coupling in salivary glands

The purpose of this study was to apply photoacoustic imaging (PAI), a relatively new imaging method, to non-invasively map neurovascular dynamics in salivary glands. Dynamic PAI with co-registered ultrasound (US) was performed in mice to monitor salivary gland hemodynamics in response to exogenous muscarinic receptor stimulation (pilocarpine) and blockade (atropine). Pilocarpine increased salivary gland oxygen saturation (%sO₂) within minutes after administration, which was abrogated by atropine. A significant correlation was observed between change in %sO₂ measured by PAI and saliva secretion. PAI is a novel imaging method that can be used for functional assessment of neurovascular dynamics in salivary glands.