Insolation-driven changes in atmospheric circulation over the past 116,000 years in subtropical Brazil

During the last glacial period, large millennial-scale temperature oscillations--the 'Dansgaard/Oeschger' cycles--were the primary climate signal in Northern Hemisphere climate archives from the high latitudes to the tropics. But whether the influence of these abrupt climate changes extended to the tropical and subtropical Southern Hemisphere, where changes in insolation are thought to be the main direct forcing of climate, has remained unclear. Here we present a high-resolution oxygen isotope record of a U/Th-dated stalagmite from subtropical southern Brazil, covering the past 116,200 years. The oxygen isotope signature varies with shifts in the source region and amount of rainfall in the area, and hence records changes in atmospheric circulation and convective intensity over South America. We find that these variations in rainfall source and amount are primarily driven by summer solar radiation, which is controlled by the Earth's precessional cycle. The Dansgaard/Oeschger cycles can be detected in our record and therefore we confirm that they also affect the tropical hydrological cycle, but that in southern subtropical Brazil, millennial-scale climate changes are not as dominant as they are in the Northern Hemisphere.     

Genome sequence and comparative analysis of the model rodent malaria parasite Plasmodium yoelii yoelii

Species of malaria parasite that infect rodents have long been used as models for malaria disease research. Here we report the whole-genome shotgun sequence of one species, Plasmodium yoelii yoelii, and comparative studies with the genome of the human malaria parasite Plasmodium falciparum clone 3D7. A synteny map of 2,212 P. y. yoelii contiguous DNA sequences (contigs) aligned to 14 P. falciparum chromosomes reveals marked conservation of gene synteny within the body of each chromosome. Of about 5,300 P. falciparum genes, more than 3,300 P. y. yoelii orthologues of predominantly metabolic function were identified. Over 800 copies of a variant antigen gene located in subtelomeric regions were found. This is the first genome sequence of a model eukaryotic parasite, and it provides insight into the use of such systems in the modelling of Plasmodium biology and disease.     

Mechanisms of self-incompatibility in flowering plants

Self-incompatibility is a widespread mechanism in flowering plants that prevents inbreeding and promotes outcrossing. The self-incompatibility response is genetically controlled by one or more multi-allelic loci, and relies on a series of complex cellular interactions between the self-incompatible pollen and pistil. Although self-incompatibility functions ultimately to prevent self-fertilization, flowering plants have evolved several unique mechanisms for rejecting the self-incompatible pollen. The self-incompatibility system in the Solanaceae makes use of a multi-allelic RNase in the pistil to block incompatible pollen tube growth. In contrast, the Papaveraceae system appears to have complex cellular responses such as calcium fluxes, actin rearrangements, and programmed cell death occurring in the incompatible pollen tube. Finally, the Brassicaceae system has a receptor kinase signalling pathway activated in the pistil leading to pollen rejection. This review highlights the recent advances made towards understanding the cellular mechanisms involved in these self-incompatibility systems and discusses the striking differences between these systems. Received 10 May 2001; received after revision 20 June 2001; accepted 20 June 2001     

Helminths of some tree frogs of the families Hylidae and Phyllomedusidae in an Atlantic rainforest fragment,Brazil

Despite the fact that Brazil is the most-studied country regarding helminths of amphibians, only around 8% of Brazilian anurans have had at least one study made of their helminth fauna. Therefore, the aim of this study was to describe the helminth community of nine species of Atlantic Rainforest anurans of two different families, eight of them with no previous study, and six of which are endemic to Brazil. The analysed hosts for their parasites were: Dendropsophus minutus (n = 48), Scinax auratus (n = 36), D. branneri (n = 33), D. elegans (n = 26), Hypsiboas albomarginatus (n = 22), Pithecopus nordestinus (n = 19), D. decipiens (n = 12), D. haddadi (n = 11) and S. x-signatus (n = 11). A total of 781 helminths were collected from 106 (48.6%) of 218 analysed hosts, 656 Centrorhyncus sp. cystacanths and 125 nematodes: 76 adults (25 Cosmocerca sp.; three Cosmocerceidae gen. sp.; 20 Cosmocerca parva, 20 Cosmocercella phyllomedusae, five Aplectana sp., two Oswaldocruzia sp. and one Rhabdias sp.), 43 encysted larvae (nine Porrocaecum sp. and 34 Brevimulticaecum sp.) and six Physaloptera sp. larvae. Anurans may display many roles within the helminth life cycles, as they act as both predator and prey to a wide variety of animals. Consequently, we have found helminths that use anurans as definitive, intermediate and paratenic hosts. Opposing other surveys in which nematodes are the most prevalent and abundant parasites, acanthocephalans were the most prevalent taxa. These findings highlight the lack of knowledge regarding the helminth fauna of anurans and reveal many gaps with respect to their infection patterns in amphibians.     

Mitochondrial activity: A possible determinant of anoxic injury in renal medulla

Summary In brain¹, heart² and kidney³, cell work in the absence of oxygen has been thought to precipitate anoxic damage by increasing the rate of depletion of cellular energy stores. In the medullary thick ascending limb of isolated perfused rat kidneys, however, reduction of ATP synthesis by a variety of mitochondrial or metabolic inhibitors caused ATP depletion comparable to that produced by oxygen deprivation but did not reproduce the lesions of anoxia. In these cells, unrestrained mitochondrial activity may be an important source of anoxic injury.     

Comparative genomics of the neglected human malaria parasite Plasmodium vivax

The human malaria parasite Plasmodium vivax is responsible for 25-40% of the approximately 515 million annual cases of malaria worldwide. Although seldom fatal, the parasite elicits severe and incapacitating clinical symptoms and often causes relapses months after a primary infection has cleared. Despite its importance as a major human pathogen, P. vivax is little studied because it cannot be propagated continuously in the laboratory except in non-human primates. We sequenced the genome of P. vivax to shed light on its distinctive biological features, and as a means to drive development of new drugs and vaccines. Here we describe the synteny and isochore structure of P. vivax chromosomes, and show that the parasite resembles other malaria parasites in gene content and metabolic potential, but possesses novel gene families and potential alternative invasion pathways not recognized previously. Completion of the P. vivax genome provides the scientific community with a valuable resource that can be used to advance investigation into this neglected species.     

The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity

The systematic translation of cancer genomic data into knowledge of tumour biology and therapeutic possibilities remains challenging. Such efforts should be greatly aided by robust preclinical model systems that reflect the genomic diversity of human cancers and for which detailed genetic and pharmacological annotation is available. Here we describe the Cancer Cell Line Encyclopedia (CCLE): a compilation of gene expression, chromosomal copy number and massively parallel sequencing data from 947 human cancer cell lines. When coupled with pharmacological profiles for 24 anticancer drugs across 479 of the cell lines, this collection allowed identification of genetic, lineage, and gene-expression-based predictors of drug sensitivity. In addition to known predictors, we found that plasma cell lineage correlated with sensitivity to IGF1 receptor inhibitors; AHR expression was associated with MEK inhibitor efficacy in NRAS-mutant lines; and SLFN11 expression predicted sensitivity to topoisomerase inhibitors. Together, our results indicate that large, annotated cell-line collections may help to enable preclinical stratification schemata for anticancer agents. The generation of genetic predictions of drug response in the preclinical setting and their incorporation into cancer clinical trial design could speed the emergence of 'personalized' therapeutic regimens.     

Visualizing heavy fermions emerging in a quantum critical Kondo lattice

In solids containing elements with f orbitals, the interaction between f-electron spins and those of itinerant electrons leads to the development of low-energy fermionic excitations with a heavy effective mass. These excitations are fundamental to the appearance of unconventional superconductivity and non-Fermi-liquid behaviour observed in actinide- and lanthanide-based compounds. Here we use spectroscopic mapping with the scanning tunnelling microscope to detect the emergence of heavy excitations with lowering of temperature in a prototypical family of cerium-based heavy-fermion compounds. We demonstrate the sensitivity of the tunnelling process to the composite nature of these heavy quasiparticles, which arises from quantum entanglement of itinerant conduction and f electrons. Scattering and interference of the composite quasiparticles is used to resolve their energy-momentum structure and to extract their mass enhancement, which develops with decreasing temperature. The lifetime of the emergent heavy quasiparticles reveals signatures of enhanced scattering and their spectral lineshape shows evidence of energy-temperature scaling. These findings demonstrate that proximity to a quantum critical point results in critical damping of the emergent heavy excitation of our Kondo lattice system.