Abnormal display of PfEMP-1 on erythrocytes carrying haemoglobin C may protect against malaria

Haemoglobin C, which carries a glutamate-to-lysine mutation in the beta-globin chain, protects West African children against Plasmodium falciparum malaria. Mechanisms of protection are not established for the heterozygous (haemoglobin AC) or homozygous (haemoglobin CC) states. Here we report a marked effect of haemoglobin C on the cell-surface properties of P. falciparum-infected erythrocytes involved in pathogenesis. Relative to parasite-infected normal erythrocytes (haemoglobin AA), parasitized AC and CC erythrocytes show reduced adhesion to endothelial monolayers expressing CD36 and intercellular adhesion molecule-1 (ICAM-1). They also show impaired rosetting interactions with non-parasitized erythrocytes, and reduced agglutination in the presence of pooled sera from malaria-immune adults. Abnormal cell-surface display of the main variable cytoadherence ligand, PfEMP-1 (P. falciparum erythrocyte membrane protein-1), correlates with these findings. The abnormalities in PfEMP-1 display are associated with markers of erythrocyte senescence, and are greater in CC than in AC erythrocytes. Haemoglobin C might protect against malaria by reducing PfEMP-1-mediated adherence of parasitized erythrocytes, thereby mitigating the effects of their sequestration in the microvasculature.     

A histone H3 methyltransferase controls DNA methylation in Neurospora crassa.

DNA methylation is involved in epigenetic processes such as X-chromosome inactivation, imprinting and silencing of transposons. We have demonstrated previously that dim-2 encodes a DNA methyltransferase that is responsible for all known cytosine methylation in Neurospora crassa. Here we report that another Neurospora gene, dim-5, is required for DNA methylation, as well as for normal growth and full fertility. We mapped dim-5 and identified it by transformation with a candidate gene. The mutant has a nonsense mutation in a SET domain of a gene related to histone methyltransferases that are involved in heterochromatin formation in other organisms. Transformation of a wild-type strain with a segment of dim-5 reactivated a silenced hph gene, apparently by 'quelling' of dim-5. We demonstrate that recombinant DIM-5 protein specifically methylates histone H3 and that replacement of lysine 9 in histone H3 with either a leucine or an arginine phenocopies the dim-5 mutation. We conclude that DNA methylation depends on histone methylation.     

Coseismic and postseismic slip of the 2011 magnitude-9 Tohoku-Oki earthquake

Most large earthquakes occur along an oceanic trench, where an oceanic plate subducts beneath a continental plate. Massive earthquakes with a moment magnitude, M(w), of nine have been known to occur in only a few areas, including Chile, Alaska, Kamchatka and Sumatra. No historical records exist of a M(w) = 9 earthquake along the Japan trench, where the Pacific plate subducts beneath the Okhotsk plate, with the possible exception of the ad 869 Jogan earthquake, the magnitude of which has not been well constrained. However, the strain accumulation rate estimated there from recent geodetic observations is much higher than the average strain rate released in previous interplate earthquakes. This finding raises the question of how such areas release the accumulated strain. A megathrust earthquake with M(w) = 9.0 (hereafter referred to as the Tohoku-Oki earthquake) occurred on 11 March 2011, rupturing the plate boundary off the Pacific coast of northeastern Japan. Here we report the distributions of the coseismic slip and postseismic slip as determined from ground displacement detected using a network based on the Global Positioning System. The coseismic slip area extends approximately 400?km along the Japan trench, matching the area of the pre-seismic locked zone. The afterslip has begun to overlap the coseismic slip area and extends into the surrounding region. In particular, the afterslip area reached a depth of approximately 100?km, with M(w) = 8.3, on 25 March 2011. Because the Tohoku-Oki earthquake released the strain accumulated for several hundred years, the paradox of the strain budget imbalance may be partly resolved. This earthquake reminds us of the potential for M(w)?≈?9 earthquakes to occur along other trench systems, even if no past evidence of such events exists. Therefore, it is imperative that strain accumulation be monitored using a space geodetic technique to assess earthquake potential.     

Klotho converts canonical FGF receptor into a specific receptor for FGF23

FGF23 is a unique member of the fibroblast growth factor (FGF) family because it acts as a hormone that derives from bone and regulates kidney functions, whereas most other family members are thought to regulate various cell functions at a local level. The renotropic activity of circulating FGF23 indicates the possible presence of an FGF23-specific receptor in the kidney. Here we show that a previously undescribed receptor conversion by Klotho, a senescence-related molecule, generates the FGF23 receptor. Using a renal homogenate, we found that Klotho binds to FGF23. Forced expression of Klotho enabled the high-affinity binding of FGF23 to the cell surface and restored the ability of a renal cell line to respond to FGF23 treatment. Moreover, FGF23 incompetence was induced by injecting wild-type mice with an anti-Klotho monoclonal antibody. Thus, Klotho is essential for endogenous FGF23 function. Because Klotho alone seemed to be incapable of intracellular signalling, we searched for other components of the FGF23 receptor and found FGFR1(IIIc), which was directly converted by Klotho into the FGF23 receptor. Thus, the concerted action of Klotho and FGFR1(IIIc) reconstitutes the FGF23 receptor. These findings provide insights into the diversity and specificity of interactions between FGF and FGF receptors.     

A simple rule for the evolution of cooperation on graphs and social networks

A fundamental aspect of all biological systems is cooperation. Cooperative interactions are required for many levels of biological organization ranging from single cells to groups of animals. Human society is based to a large extent on mechanisms that promote cooperation. It is well known that in unstructured populations, natural selection favours defectors over cooperators. There is much current interest, however, in studying evolutionary games in structured populations and on graphs. These efforts recognize the fact that who-meets-whom is not random, but determined by spatial relationships or social networks. Here we describe a surprisingly simple rule that is a good approximation for all graphs that we have analysed, including cycles, spatial lattices, random regular graphs, random graphs and scale-free networks: natural selection favours cooperation, if the benefit of the altruistic act, b, divided by the cost, c, exceeds the average number of neighbours, k, which means b/c > k. In this case, cooperation can evolve as a consequence of 'social viscosity' even in the absence of reputation effects or strategic complexity.     

Reductive evolution suggested from the complete genome sequence of a plant-pathogenic phytoplasma

The minimal gene set essential for life has long been sought. We report the 860-kb genome of the obligate intracellular plant pathogen phytoplasma (Candidatus Phytoplasma asteris, OY strain). The phytoplasma genome encodes even fewer metabolic functions than do mycoplasma genomes. It lacks the pentose phosphate cycle and, more unexpectedly, ATP-synthase subunits, which are thought to be essential for life. This may be the result of reductive evolution as a consequence of life as an intracellular parasite in a nutrient-rich environment.     

Prediction of final data with use of preliminary and/or revised data

In the case of US national accounts the data are revised for the first few years and every decade, which implies that we do not really have the final data. In this paper we aim to predict the final data, using the preliminary data and/or the revised data. The following predictors are introduced and derived from a context of the non-linear filtering or smoothing problem, which are: (1) prediction of the final data of time t given the preliminary data up to time t- 1, (2) prediction of the final data of time t given the preliminary data up to time t, (3) prediction of the final data of time t given the preliminary data up to time T, (4) prediction of the final data of time t given the revised data up to time t -1 and the preliminary data up to time t- 1, and (5) prediction of the final data of time t given the revised data up to time t-1 and the preliminary data up to time t. It is shown that (5) is the best predictor but not too different from (3). The prediction problem is illustrated using US per capita consumption data.