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.     

Discovery of X-rays from the protostellar outflow object HH2

Herbig-Haro (HH) objects have been known for 50 years to be luminous condensations of gas in star-forming regions, but their underlying physical nature is still being elucidated. Previously suggested models encompass newborn stars, stellar winds clashing with nebular material, dense pockets of interstellar gas excited by shocks from outflows, and interstellar 'bullets' (ref. 6). Recent progress has been made with the jet-induced shock model, in which material streams out of young stellar objects and collides with the surrounding interstellar medium. A clear prediction of this model is that the most energetic Herbig-Haro objects will emit X-rays, although they have not hitherto been detected. Here we report the discovery of X-ray emission from one of the brightest and closest Herbig-Haro objects, HH2, at a level consistent with the model predictions. We conclude that this Herbig-Haro object contains shock-heated material located at or near its leading edge with a temperature of about 106 K.     

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.     

Thin-film thermoelectric devices with high room-temperature figures of merit

Thermoelectric materials are of interest for applications as heat pumps and power generators. The performance of thermoelectric devices is quantified by a figure of merit, ZT, where Z is a measure of a material's thermoelectric properties and T is the absolute temperature. A material with a figure of merit of around unity was first reported over four decades ago, but since then-despite investigation of various approaches-there has been only modest progress in finding materials with enhanced ZT values at room temperature. Here we report thin-film thermoelectric materials that demonstrate a significant enhancement in ZT at 300 K, compared to state-of-the-art bulk Bi2Te3 alloys. This amounts to a maximum observed factor of approximately 2.4 for our p-type Bi2Te3/Sb2Te3 superlattice devices. The enhancement is achieved by controlling the transport of phonons and electrons in the superlattices. Preliminary devices exhibit significant cooling (32 K at around room temperature) and the potential to pump a heat flux of up to 700 W cm-2; the localized cooling and heating occurs some 23,000 times faster than in bulk devices. We anticipate that the combination of performance, power density and speed achieved in these materials will lead to diverse technological applications: for example, in thermochemistry-on-a-chip, DNA microarrays, fibre-optic switches and microelectrothermal systems.     

Transformation: a tool for studying fungal pathogens of plants

Plant diseases caused by plant pathogenic fungi continuously threaten the sustainability of global crop production. An effective way to study the disease-causing mechanisms of these organisms is to disrupt their genes, in both a targeted and random manner, so as to isolate mutants exhibiting altered virulence. Although a number of techniques have been employed for such an analysis, those based on transformation are by far the most commonly used. In filamentous fungi, the introduction of DNA by transformation typically results in either the heterologous (illegitimate) integration or the homologous integration of the transforming DNA into the target genome. Homologous integration permits a targeted gene disruption by replacing the wild-type allele on the genome with a mutant allele on transforming DNA. This process has been widely used to determine the role of newly isolated fungal genes in pathogenicity. The heterologous integration of transforming DNA causes a random process of gene disruption (insertional mutagenesis) and has led to the isolation of many fungal mutants defective in pathogenicity. A big advantage of insertional mutagenesis over the more traditional chemical or radiation mutagenesis procedures is that the mutated gene is tagged by transforming DNA and can subsequently be cloned using the transforming DNA. The application of various transformation-based techniques for fungal gene manipulation and how they have increased our understanding and appreciation of some of the most serious plant pathogenic fungi are discussed. Received 9 May 2001; received after revision 2 July 2001; accepted 3 July 2001