PCR amplification of the Irish potato famine pathogen from historic specimens

Late blight, caused by the oomycete plant pathogen Phytophthora infestans, is a devastating disease of potato and was responsible for epidemics that led to the Irish potato famine in 1845 (refs 1,2,3,4,5). Before the 1980s, worldwide populations of P. infestans were dominated by a single clonal lineage, the US-1 genotype or Ib mitochondrial DNA (mtDNA) haplotype, and sexual reproduction was not documented outside Mexico, the centre of diversity of the pathogen. Here we describe the amplification and sequencing of 100-base-pair fragments of DNA from the internal transcribed spacer region 2 from 28 historic herbarium samples including Irish and British samples collected between 1845 and 1847, confirming the identity of the pathogen. We amplified a variable region of mtDNA that is present in modern Ib haplotypes of P. infestans, but absent in the other known modern haplotypes (Ia, IIa and IIb). Lesions in samples tested were not caused by the Ib haplotype of P. infestans, and so theories that assume that the Ib haplotype is the ancestral strain need to be re-evaluated. Our data emphasize the importance of using historic specimens when making inferences about historic populations.     

A freely diffusible form of Sonic hedgehog mediates long-range signalling

The secreted protein Sonic hedgehog (Shh) exerts many of its patterning effects through a combination of short- and long-range signalling. Three distinct mechanisms, which are not necessarily mutually exclusive, have been proposed to account for the long-range effects of Shh: simple diffusion of Shh, a relay mechanism in which Shh activates secondary signals, and direct delivery of Shh through cytoplasmic extensions, termed cytonemes. Although there is much data (using soluble recombinant Shh (ShhN)) to support the simple diffusion model of long-range Shh signalling, there has been little evidence to date for a native form of Shh that is freely diffusible and not membrane-associated. Here we provide evidence for a freely diffusible form of Shh (s-ShhNp) that is cholesterol modified, multimeric and biologically potent. We further demonstrate that the availability of s-ShhNp is regulated by two functional antagonists of the Shh pathway, Patched (Ptc) and Hedgehog-interacting protein (Hip). Finally, we show a gradient of s-ShhNp across the anterior-posterior axis of the chick limb, demonstrating the physiological relevance of s-ShhNp.     

Antibacterial agents based on the cyclic D,L-alpha-peptide architecture

The rapid emergence of bacterial infections that are resistant to many drugs underscores the need for new therapeutic agents. Here we report that six- and eight-residue cyclic d,l-alpha-peptides act preferentially on Gram-positive and/or Gram-negative bacterial membranes compared to mammalian cells, increase membrane permeability, collapse transmembrane ion potentials, and cause rapid cell death. The effectiveness of this class of materials as selective antibacterial agents is highlighted by the high efficacy observed against lethal methicillin-resistant Staphylococcus aureus infections in mice. Cyclic d,l-alpha-peptides are proteolytically stable, easy to synthesize, and can be derived from a potentially vast membrane-active sequence space. The unique abiotic structure of the cyclic peptides and their quick bactericidal action may also contribute to limit temporal acquirement of drug resistant bacteria. The low molecular weight d,l-alpha-peptides offer an attractive complement to the current arsenal of naturally derived antibiotics, and hold considerable potential in combating a variety of existing and emerging infectious diseases.     

Deep-sea ecology. Developmental arrest in vent worm embryos

Temperature is a key factor in controlling the distribution of marine organisms and is particularly important at hydrothermal vents, where steep thermal gradients are present over a scale of centimetres. The thermophilic worm Alvinella pompejana, which is found at the vents of the East Pacific Rise (2,500-m depth), has an unusually broad thermotolerance (20-80 degrees C) as an adult, but we show here that the temperature range required by the developing embryo is very different from that tolerated by adults. Our results indicate that early embryos may disperse through cold abyssal water in a state of developmental arrest, completing their development only when they encounter water that is warm enough for their growth and survival.     

Haemoglobin C protects against clinical Plasmodium falciparum malaria.

Haemoglobin C (HbC; beta6Glu --> Lys) is common in malarious areas of West Africa, especially in Burkina Faso. Conclusive evidence exists on the protective role against severe malaria of haemoglobin S (HbS; beta6Glu --> Val) heterozygosity, whereas conflicting results for the HbC trait have been reported and no epidemiological data exist on the possible role of the HbCC genotype. In vitro studies suggested that HbCC erythrocytes fail to support the growth of P. falciparum but HbC homozygotes with high P. falciparum parasitaemias have been observed. Here we show, in a large case-control study performed in Burkina Faso on 4,348 Mossi subjects, that HbC is associated with a 29% reduction in risk of clinical malaria in HbAC heterozygotes (P = 0.0008) and of 93% in HbCC homozygotes (P = 0.0011). These findings, together with the limited pathology of HbAC and HbCC compared to the severely disadvantaged HbSS and HbSC genotypes and the low betaS gene frequency in the geographic epicentre of betaC, support the hypothesis that, in the long term and in the absence of malaria control, HbC would replace HbS in central West Africa.     

Converting currencies in the Old World

Raw materials recovered from archaeological excavations in the Indus Valley, the Persian Gulf, Mesopotamia, Egypt and the eastern Mediterranean reflect the existence of long-distance trading during the Bronze Age, which united these regions into networks of commercial exchange. As each region relied on a different set of weights for trading, a straightforward conversion system must have been in operation. Here we describe a simple and universal conversion system that could have provided an economic key to the trade networks of the Old World between 2500 and 1000 bc.