Genetic diversity and chloroquine selective sweeps in Plasmodium falciparum

Widespread use of antimalarial agents can profoundly influence the evolution of the human malaria parasite Plasmodium falciparum. Recent selective sweeps for drug-resistant genotypes may have restricted the genetic diversity of this parasite, resembling effects attributed in current debates to a historic population bottleneck. Chloroquine-resistant (CQR) parasites were initially reported about 45 years ago from two foci in southeast Asia and South America, but the number of CQR founder mutations and the impact of chlorquine on parasite genomes worldwide have been difficult to evaluate. Using 342 highly polymorphic microsatellite markers from a genetic map, here we show that the level of genetic diversity varies substantially among different regions of the parasite genome, revealing extensive linkage disequilibrium surrounding the key CQR gene pfcrt and at least four CQR founder events. This disequilibrium and its decay rate in the pfcrt-flanking region are consistent with strong directional selective sweeps occurring over only approximately 20-80 sexual generations, especially a single resistant pfcrt haplotype spreading to very high frequencies throughout most of Asia and Africa. The presence of linkage disequilibrium provides a basis for mapping genes under drug selection in P. falciparum.     

Out of Africa again and again

The publication of a haplotype tree of human mitochondrial DNA variation in 1987 provoked a controversy about the details of recent human evolution that continues to this day. Now many haplotype trees are available, and new analytical techniques exist for testing hypotheses about recent evolutionary history using haplotype trees. Here I present formal statistical analysis of human haplotype trees for mitochondrial DNA, Y-chromosomal DNA, two X-linked regions and six autosomal regions. A coherent picture of recent human evolution emerges with two major themes. First is the dominant role that Africa has played in shaping the modern human gene pool through at least two--not one--major expansions after the original range extension of Homo erectus out of Africa. Second is the ubiquity of genetic interchange between human populations, both in terms of recurrent gene flow constrained by geographical distance and of major population expansion events resulting in interbreeding, not replacement.     

Cdc42 regulates GSK-3beta and adenomatous polyposis coli to control cell polarity

Cell polarity is a fundamental property of all cells. In higher eukaryotes, the small GTPase Cdc42, acting through a Par6-atypical protein kinase C (aPKC) complex, is required to establish cellular asymmetry during epithelial morphogenesis, asymmetric cell division and directed cell migration. However, little is known about what lies downstream of this complex. Here we show, through the use of primary rat astrocytes in a cell migration assay, that Par6-PKCzeta interacts directly with and regulates glycogen synthase kinase-3beta (GSK-3beta) to promote polarization of the centrosome and to control the direction of cell protrusion. Cdc42-dependent phosphorylation of GSK-3beta occurs specifically at the leading edge of migrating cells, and induces the interaction of adenomatous polyposis coli (Apc) protein with the plus ends of microtubules. The association of Apc with microtubules is essential for cell polarization. We conclude that Cdc42 regulates cell polarity through the spatial regulation of GSK-3beta and Apc. This role for Apc may contribute to its tumour-suppressor activity.     

Enhancements of energetic particles near the heliospheric termination shock

The spacecraft Voyager 1 is at a distance greater than 85 au from the Sun, in the vicinity of the termination shock that marks the abrupt slowing of the supersonic solar wind and the beginning of the extended and unexplored distant heliosphere. This shock is expected to accelerate 'anomalous cosmic rays', as well as to re-accelerate Galactic cosmic rays and low-energy particles from the inner Solar System. Here we report a significant increase in the numbers of energetic ions and electrons that persisted for seven months beginning in mid-2002. This increase differs from any previously observed in that there was a simultaneous increase in Galactic cosmic ray ions and electrons, anomalous cosmic rays and low-energy ions. The low-intensity level and spectral energy distribution of the anomalous cosmic rays, however, indicates that Voyager 1 still has not reached the termination shock. Rather, the observed increase is an expected precursor event. We argue that the radial anisotropy of the cosmic rays is expected to be small in the foreshock region, as is observed.     

Motion-induced spatial conflict

Borders defined by small changes in brightness (luminance contrast) or by differences in colour (chromatic contrast) appear to move more slowly than those defined by strong luminance contrast. As spatial coding is influenced by motion, if placed in close proximity, the different types of moving border might appear to drift apart. Using this configuration, we show here that observers instead report a clear illusory spatial jitter of the low-luminance-contrast boundary. This visible interaction between motion and spatial-position coding occurred at a characteristic rate (approximately 22.3 Hz), although the stimulus motion was continuous and invariant. The jitter rate did not vary with the speed of movement. The jitter was not due to small involuntary movements of the eyes, because it only occurred at a specific point within the stimulus, the low-luminance-contrast boundary. These findings show that the human visual system contains a neural mechanism that periodically resolves the spatial conflict created by adjacent moving borders that have the same physical but different perceptual speeds.