Analysis of Plasmodium falciparum diversity in natural infections by deep sequencing

Malaria elimination strategies require surveillance of the parasite population for genetic changes that demand a public health response, such as new forms of drug resistance. Here we describe methods for the large-scale analysis of genetic variation in Plasmodium falciparum by deep sequencing of parasite DNA obtained from the blood of patients with malaria, either directly or after short-term culture. Analysis of 86,158 exonic single nucleotide polymorphisms that passed genotyping quality control in 227 samples from Africa, Asia and Oceania provides genome-wide estimates of allele frequency distribution, population structure and linkage disequilibrium. By comparing the genetic diversity of individual infections with that of the local parasite population, we derive a metric of within-host diversity that is related to the level of inbreeding in the population. An open-access web application has been established for the exploration of regional differences in allele frequency and of highly differentiated loci in the P.?falciparum genome.     

Stochastic yet biased expression of multiple Dscam splice variants by individual cells

The Drosophila melanogaster gene Dscam is essential for axon guidance and has 38,016 possible alternative splice forms. This diversity can potentially be used to distinguish cells. We analyzed the Dscam mRNA isoforms expressed by different cell types and individual cells. The choice of splice variants expressed is regulated both spatially and temporally. Different subtypes of photoreceptors express broad yet distinctive spectra of Dscam isoforms. Single-cell RT-PCR documented that individual cells express several different Dscam isoforms and allowed an estimation of the diversity that is present. For example, we estimate that each R3/R4 photoreceptor cell expresses 14-50 distinct mRNAs chosen from the spectrum of thousands of splice variants distinctive of its cell type. Thus, the Dscam repertoire of each cell is different from those of its neighbors, providing a potential mechanism for generating unique cell identity in the nervous system and elsewhere.     

Mutations in SLC6A19, encoding B0AT1, cause Hartnup disorder

Hartnup disorder, an autosomal recessive defect named after an English family described in 1956 (ref. 1), results from impaired transport of neutral amino acids across epithelial cells in renal proximal tubules and intestinal mucosa. Symptoms include transient manifestations of pellagra (rashes), cerebellar ataxia and psychosis. Using homozygosity mapping in the original family in whom Hartnup disorder was discovered, we confirmed that the critical region for one causative gene was located on chromosome 5p15 (ref. 3). This region is homologous to the area of mouse chromosome 13 that encodes the sodium-dependent amino acid transporter B(0)AT1 (ref. 4). We isolated the human homolog of B(0)AT1, called SLC6A19, and determined its size and molecular organization. We then identified mutations in SLC6A19 in members of the original family in whom Hartnup disorder was discovered and of three Japanese families. The protein product of SLC6A19, the Hartnup transporter, is expressed primarily in intestine and renal proximal tubule and functions as a neutral amino acid transporter.     

The nonlinear nature of friction

Tribology is the study of adhesion, friction, lubrication and wear of surfaces in relative motion. It remains as important today as it was in ancient times, arising in the fields of physics, chemistry, geology, biology and engineering. The more we learn about tribology the more complex it appears. Nevertheless, recent experiments coupled to theoretical modelling have made great advances in unifying apparently diverse phenomena and revealed many subtle and often non-intuitive aspects of matter in motion, which stem from the nonlinear nature of the problem.     

Experimental demonstration of quantum memory for light

The information carrier of today's communications, a weak pulse of light, is an intrinsically quantum object. As a consequence, complete information about the pulse cannot be perfectly recorded in a classical memory, even in principle. In the field of quantum information, this has led to the long-standing challenge of how to achieve a high-fidelity transfer of an independently prepared quantum state of light onto an atomic quantum state. Here we propose and experimentally demonstrate a protocol for such a quantum memory based on atomic ensembles. Recording of an externally provided quantum state of light onto the atomic quantum memory is achieved with 70 per cent fidelity, significantly higher than the limit for classical recording. Quantum storage of light is achieved in three steps: first, interaction of the input pulse and an entangling field with spin-polarized caesium atoms; second, subsequent measurement of the transmitted light; and third, feedback onto the atoms using a radio-frequency magnetic pulse conditioned on the measurement result. The density of recorded states is 33 per cent higher than the best classical recording of light onto atoms, with a quantum memory lifetime of up to 4 milliseconds.