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A macrophage attacking bacteria. Macrophages are phagocytic cells found in blood, lymph and in all mammalian tissue types. They have many and diverse roles in normal development, homeostasis, tissue repair and the immune response to pathogens. Their diversity means that they are involved in almost every human disease and are prime therapeutic targets because their function can be augmented or inhibited to alter disease outcome. A Review in this issue discusses macrophage physiology in terms of the homeostatic mechanisms by which macrophages contribute to physiological and pathophysiologic adaptations in mammals. Cover: SCIEPRO/SCIENCE PHOTO LIBRARY
China’s well-handled response to outbreaks of H7N9 avian influenza belies the country’s bad reputation from its past dealings with disease. But there are still improvements to be made.
This week in science: Ricin-laced letters sent to politicians; Antares rocket completes its maiden test flight; and Nobel laureate François Jacob dies.
On the 60th anniversary of the double helix, we should admit that we don't fully understand how evolution works at the molecular level, suggests Philip Ball.
Physicists have come up with a way to characterize and command untrusted quantum systems. Two experts discuss the significance of these findings for fundamental science and for practical quantum computation and cryptography. See Article p.456
The ability of sodium chloride to induce enzymatic activity that leads to the generation of pathogenic TH17 immune cells implicates salt as a possible factor that might exacerbate autoimmune disease. See Letters p.513 & p.518
The discovery of a particle that looked like the Higgs boson marked a milestone for physics. Results reported since then are strikingly consistent with expectations for the Higgs particle of the minimal standard model of particle physics.
More than 30 years since the AIDS pandemic began, there is still no effective vaccine. But analysis of broadly acting, potent human antibodies obtained from single cells suggests a rational approach to vaccine development. See Article p.469
A new approach has been used to image magnetic fields in living cells of magnetotactic bacteria. The technique could be applied to study the dynamics of magnetism in other biological systems. See Letter p.486
The reported sequence of the zebrafish genome, together with the production of mutant strains representing more than one-third of all its protein-coding regions, will accelerate the characterization of human genes. See Letters p.494 & p.498
A discussion of progress in macrophage biology, examining their classification, diverse lineages, identities and regulation, their roles in regulating normal physiology and development, and their identification as therapeutic targets in human diseases.
A scheme is described that enables characterization and classical command of large quantum systems; it provides a test of whether a claimed quantum computer is truly quantum, and also advances towards a goal of quantum cryptography, namely the use of untrusted devices to establish a shared random key, with security based on the validity of quantum physics.
A global view of the genetic networks regulating the differentiation of TH17 cells is presented, based on temporal expression profiling, computational network reconstruction and validation of predicted interactions by nanowire-mediated siRNA perturbation.
Longitudinal sampling is used to map the evolution of an HIV-1 virus from the time of infection, and the co-evolution of a broadly neutralizing antibody in the same infected patient; the findings have important implications for HIV vaccine development.
Small-angle scattering of X-rays or neutrons is more readily applied to macromolecular complexes than is X-ray crystallography, and is particularly useful for protein complexes with high flexibility; here new quantitative metrics are presented that will allow solution-derived structures to be validated and assessed for mass, resolution and accuracy.
Microwave stimulation of a superconducting artificial three-level atom is used to demonstrate high-fidelity, non-Abelian geometric transformations, the results of which depend on the order in which they are performed.
Mass-independent fractionation of sulphur isotopes in basalts from the oceanic island of Mangaia (Cook Islands) indicates ancient subducted Archaean (>2.45 Gyr) oceanic crust and lithosphere survives in the mantle to be sampled beneath hotspot volcanoes.
A project to identify the phenotypes of disruptive mutations in every zebrafish protein-coding gene has so far revealed potentially disruptive mutations in more than 38% of the protein-coding genes, and the phenotypic consequences of each allele can be assessed using a novel multi-allelic phenotyping scheme.
A high-quality sequence assembly of the zebrafish genome reveals the largest gene set of any vertebrate and provides information on key genomic features, and comparison to the human reference genome shows that approximately 70% of human protein-coding genes have at least one clear zebrafish orthologue.
The public health burden of dengue is unknown; here cartographic approaches are used to provide insight into the global, regional and national burden of dengue, with the finding that the global number of infections per year is around 390 million, more than three times the estimate of the World Health Organization.
A functionally diverse superfamily of bacterial phospholipase enzymes that mediate antagonisitc interactions as effectors of the type VI secretion system is uncovered; these enzymes degrade the bacterial membrane, representing a novel mechanism of bacterial competition.
Transcriptional profiling of developing TH17 cells identifies serum glucocorticoid kinase 1 (SGK1) as an essential node downstream of IL-23 signalling, and transcriptional analysis shows that a modest increase in salt concentration induces SGK1 expression, promotes IL-23 receptor expression and enhances TH17 cell differentiation, accelerating the development of autoimmunity.
Increased salt concentrations are shown to induce murine and human TH17 cells by a mechanism that depends on activation of p38/MAPK, NFAT5 and SGK1; mice kept on a high-salt diet develop a more severe experimental autoimmune encephalomyelitis due to increased induction of TH17 cells.
ICOS ligand expression by bystander B cells is shown to induce pseudopod extension and migration of CXCR5-expressing T-helper cells into B-cell follicles, where they provide help to cognate B cells for germinal centre development.
Saccharomyces cerevisiae is engineered to produce high concentrations of artemisinic acid, a precursor of the artemisinin used in combination therapies for malaria treatment; an efficient and practical chemical process to convert artemisinic acid to artemisinin is also developed.
The X-ray crystal structure of a high-affinity phosphate importer in an inward-facing, occluded state in the presence of phosphate is reported; this is the first structure of a membrane protein involved in inorganic phosphate uptake and the first crystal structure of a eukaryotic MFS transporter.