Restoration of tolerance in lupus by targeted inhibitory receptor expression

Lupus, a multigenic autoimmune condition in which a breakdown of tolerance results in the development of autoantibodies, leads to a variety of pathologic outcomes. Despite the heterogeneity of factors influencing disease susceptibility, we demonstrate that the partial restoration of inhibitory Fc receptor (FcgRIIB) levels on B cells in lupus-prone mouse strains is sufficient to restore tolerance and prevent autoimmunity. FcgRIIB regulates a common B cell checkpoint in genetically diverse lupus-prone mouse strains, and modest changes in its expression can result in either tolerance or autoimmunity. Therefore, increasing FcgammaRIIB levels on B cells may be an effective way to treat autoimmune diseases.     

Simulations of jets driven by black hole rotation

The origin of jets emitted from black holes is not well understood; however, there are two possible energy sources: the accretion disk or the rotating black hole. Magnetohydrodynamic simulations show a well-defined jet that extracts energy from a black hole. If plasma near the black hole is threaded by large-scale magnetic flux, it will rotate with respect to asymptotic infinity, creating large magnetic stresses. These stresses are released as a relativistic jet at the expense of black hole rotational energy. The physics of the jet initiation in the simulations is described by the theory of black hole gravitohydromagnetics.     

Erasing the world's slow stain: strategies to beat multidrug-resistant tuberculosis

Multidrug-resistant tuberculosis (MDR) is perceived as a growing hazard to human health worldwide. Judgments about the true scale of the problem, and strategies for containing it, need to come from a balanced appraisal of the epidemiological evidence. We conclude in this review that MDR is, and will probably remain, a locally severe problem; that epidemics can be prevented by fully exploiting the potential of standard short-course chemotherapy (SCC) based on cheap and safe first-line drugs; and that best-practice SCC may even reduce the incidence of MDR where it has already become endemic. On the basis of the available, imperfect data, we recommend a three-part response to the threat of MDR: widespread implementation of SCC as the cornerstone of good tuberculosis control, improved resistance testing and surveillance, and the careful introduction of second-line drugs after a sound evaluation of cost, effectiveness, and feasibility.     

Comparative genomics of trypanosomatid parasitic protozoa

A comparison of gene content and genome architecture of Trypanosoma brucei, Trypanosoma cruzi, and Leishmania major, three related pathogens with different life cycles and disease pathology, revealed a conserved core proteome of about 6200 genes in large syntenic polycistronic gene clusters. Many species-specific genes, especially large surface antigen families, occur at nonsyntenic chromosome-internal and subtelomeric regions. Retroelements, structural RNAs, and gene family expansion are often associated with syntenic discontinuities that-along with gene divergence, acquisition and loss, and rearrangement within the syntenic regions-have shaped the genomes of each parasite. Contrary to recent reports, our analyses reveal no evidence that these species are descended from an ancestor that contained a photosynthetic endosymbiont.     

Ultrahigh-density nanowire lattices and circuits

We describe a general method for producing ultrahigh-density arrays of aligned metal and semiconductor nanowires and nanowire circuits. The technique is based on translating thin film growth thickness control into planar wire arrays. Nanowires were fabricated with diameters and pitches (center-to-center distances) as small as 8 nanometers and 16 nanometers, respectively. The nanowires have high aspect ratios (up to 10(6)), and the process can be carried out multiple times to produce simple circuits of crossed nanowires with a nanowire junction density in excess of 10(11) per square centimeter. The nanowires can also be used in nanomechanical devices; a high-frequency nanomechanical resonator is demonstrated.     

Paucity of genes on the Drosophila X chromosome showing male-biased expression

Sex chromosomes are primary determinants of sexual dimorphism in many organisms. These chromosomes are thought to arise via the divergence of an ancestral autosome pair and are almost certainly influenced by differing selection in males and females. Exploring how sex chromosomes differ from autosomes is highly amenable to genomic analysis. We examined global gene expression in Drosophila melanogaster and report a dramatic underrepresentation of X-chromosome genes showing high relative expression in males. Using comparative genomics, we find that these same X-chromosome genes are exceptionally poorly conserved in the mosquito Anopheles gambiae. These data indicate that the X chromosome is a disfavored location for genes selectively expressed in males.