Phagocytosis and clearance of apoptotic cells is mediated by MER

Apoptosis is fundamental to the development and maintenance of animal tissues and the immune system. Rapid clearance of apoptotic cells by macrophages is important to inhibit inflammation and autoimmune responses against intracellular antigens. Here we report a new function for Mer, a member of the Axl/Mer/Tyro3 receptor tyrosine kinase family. mer(kd) mice with a cytoplasmic truncation of Mer had macrophages deficient in the clearance of apoptotic thymocytes. This was corrected in chimaeric mice reconstituted with bone marrow from wild-type animals. Primary macrophages isolated from mer(kd) mice showed that the phagocytic deficiency was restricted to apoptotic cells and was independent of Fc receptor-mediated phagocytosis or ingestion of other particles. The inability to clear apoptotic cells adequately may be linked to an increased number of nuclear autoantibodies in mer(kd) mice. Thus, the Mer receptor tyrosine kinase seems to be critical for the engulfment and efficient clearance of apoptotic cells. This has implications for inflammation and autoimmune diseases such as systemic lupus erythematosus.     

Scalable architecture in mammalian brains

Comparison of mammalian brain parts has often focused on differences in absolute size, revealing only a general tendency for all parts to grow together. Attempts to find size-independent effects using body weight as a reference variable obscure size relationships owing to independent variation of body size and give phylogenies of questionable significance. Here we use the brain itself as a size reference to define the cerebrotype, a species-by-species measure of brain composition. With this measure, across many mammalian taxa the cerebellum occupies a constant fraction of the total brain volume (0.13 +/- 0.02), arguing against the hypothesis that the cerebellum acts as a computational engine principally serving the neocortex. Mammalian taxa can be well separated by cerebrotype, thus allowing the use of quantitative neuroanatomical data to test evolutionary relationships. Primate cerebrotypes have progressively shifted and neocortical volume fractions have become successively larger in lemurs and lorises, New World monkeys, Old World monkeys, and hominoids, lending support to the idea that primate brain architecture has been driven by directed selection pressure. At the same time, absolute brain size can vary over 100-fold within a taxon, while maintaining a relatively uniform cerebrotype. Brains therefore constitute a scalable architecture.     

Linkage disequilibrium in the human genome

With the availability of a dense genome-wide map of single nucleotide polymorphisms (SNPs), a central issue in human genetics is whether it is now possible to use linkage disequilibrium (LD) to map genes that cause disease. LD refers to correlations among neighbouring alleles, reflecting 'haplotypes' descended from single, ancestral chromosomes. The size of LD blocks has been the subject of considerable debate. Computer simulations and empirical data have suggested that LD extends only a few kilobases (kb) around common SNPs, whereas other data have suggested that it can extend much further, in some cases greater than 100 kb. It has been difficult to obtain a systematic picture of LD because past studies have been based on only a few (1-3) loci and different populations. Here, we report a large-scale experiment using a uniform protocol to examine 19 randomly selected genomic regions. LD in a United States population of north-European descent typically extends 60 kb from common alleles, implying that LD mapping is likely to be practical in this population. By contrast, LD in a Nigerian population extends markedly less far. The results illuminate human history, suggesting that LD in northern Europeans is shaped by a marked demographic event about 27,000-53,000 years ago.     

Crystal structure of a hairpin ribozyme-inhibitor complex with implications for catalysis

The hairpin ribozyme catalyses sequence-specific cleavage of RNA. The active site of this natural RNA results from the docking of two irregular helices: stems A and B. One strand of stem A harbours the scissile bond. The 2.4 A resolution structure of a hairpin ribozyme-inhibitor complex reveals that the ribozyme aligns the 2'-OH nucleophile and the 5'-oxo leaving group by twisting apart the nucleotides that flank the scissile phosphate. The base of the nucleotide preceding the cleavage site is stacked within stem A; the next nucleotide, a conserved guanine, is extruded from stem A and accommodated by a highly complementary pocket in the minor groove of stem B. Metal ions are absent from the active site. The bases of four conserved purines are positioned potentially to serve as acid-base catalysts. This is the first structure determination of a fully assembled ribozyme active site that catalyses a phosphodiester cleavage without recourse to metal ions.     

An auroral flare at Jupiter

Jupiter's aurora is the most powerful in the Solar System. It is powered largely by energy extracted from planetary rotation, although there seems also to be a contribution from the solar wind. This contrasts with Earth's aurora, which is generated through the interaction of the solar wind with the magnetosphere. The major features of Jupiter's aurora (based on far-ultraviolet, near-infrared and visible-wavelength observations) include a main oval that generally corotates with the planet and a region of patchy, diffuse emission inside the oval on Jupiter's dusk side. Here we report the discovery of a rapidly evolving, very bright and localized emission poleward of the northern main oval, in a region connected magnetically to Jupiter's outer magnetosphere. The intensity of the emission increased by a factor of 30 within 70 s, and then decreased on a similar timescale, all captured during a single four-minute exposure. This type of flaring emission has not previously been reported for Jupiter (similar, but smaller, transient events have been observed at Earth), and it may be related directly to changes in the solar wind.     

Superconductivity in the non-oxide perovskite MgCNi3

The interplay of magnetic interactions, the dimensionality of the crystal structure and electronic correlations in producing superconductivity is one of the dominant themes in the study of the electronic properties of complex materials. Although magnetic interactions and two-dimensional structures were long thought to be detrimental to the formation of a superconducting state, they are actually common features of both the high transition-temperature (Tc) copper oxides and low-Tc material Sr2RuO4, where they appear to be essential contributors to the exotic electronic states of these materials. Here we report that the perovskite-structured compound MgCNi3 is superconducting with a critical temperature of 8 K. This material is the three-dimensional analogue of the LnNi2B2C family of superconductors, which have critical temperatures up to 16 K (ref. 2). The itinerant electrons in both families of materials arise from the partial filling of the nickel d-states, which generally leads to ferromagnetism as is the case in metallic Ni. The high relative proportion of Ni in MgCNi3 suggests that magnetic interactions are important, and the lower Tc of this three-dimensional compound-when compared to the LnNi2B2C family-contrasts with conventional ideas regarding the origins of superconductivity.     

A massive reservoir of low-excitation molecular gas at high redshift

Molecular hydrogen (H2) is an important component of galaxies because it fuels star formation and the accretion of gas onto active galactic nuclei (AGN), the two processes that can generate the large infrared luminosities of gas-rich galaxies. Observations of spectral-line emission from the tracer molecule carbon monoxide (CO) are used to probe the properties of this gas. But the lines that have been studied in the local Universe-mostly the lower rotational transitions of J = 1 --> 0 and J = 2 --> 1-have hitherto been unobservable in high-redshift galaxies. Instead, higher transitions have been used, although the densities and temperatures required to excite these higher transitions may not be reached by much of the gas. As a result, past observations may have underestimated the total amount of molecular gas by a substantial amount. Here we report the discovery of large amounts of low-excitation molecular gas around the infrared-luminous quasar APM08279+5255 at redshift z = 3.91, using the two lowest excitation lines of 12 CO (J = 1 --> 0 and J = 2 --> 1). The maps confirm the presence of hot and dense gas near the nucleus, and reveal an extended reservoir of molecular gas with low excitation that is 10 to 100 times more massive than the gas traced by the higher-excitation observations. This raises the possibility that significant amounts of low-excitation molecular gas may exist in the environments of high-redshift (z > 3) galaxies.     

ICOS is essential for effective T-helper-cell responses

The outcome of T-cell responses after T-cell encounter with specific antigens is modulated by co-stimulatory signals, which are required for both lymphocyte activation and development of adaptive immunity. ICOS, an inducible co-stimulator with homology to CD28, is expressed on activated, but not resting T cells, and shows T-cell co-stimulatory function in vitro. ICOS binds specifically to its counter-receptor B7RP-1 (refs 5,6,7), but not to B7-1 or B7-2. Here we provide in vivo genetic evidence that ICOS delivers a co-stimulatory signal that is essential both for efficient interaction between T and B cells and for normal antibody responses to T-cell-dependent antigens. To determine the physiological function of ICOS, we generated and characterized gene-targeted ICOS-deficient mice. In vivo, a lack of ICOS results in severely deficient T-cell-dependent B-cell responses. Germinal centre formation is impaired and immunoglobulin class switching, including production of allergy-mediating IgE, is defective. ICOS-deficient T cells primed in in vivo and restimulated in vitro with specific antigen produce only low levels of interleukin-4, but remain fully competent to produce interferon-gamma.     

Palaeovegetation. Diversity of temperate plants in east Asia

The exceptionally broad species diversity of vascular plant genera in east Asian temperate forests, compared with their sister taxa in North America, has been attributed to the greater climatic diversity of east Asia, combined with opportunities for allopatric speciation afforded by repeated fragmentation and coalescence of populations through Late Cenozoic ice-age cycles. According to Qian and Ricklefs, these opportunities occurred in east Asia because temperate forests extended across the continental shelf to link populations in China, Korea and Japan during glacial periods, whereas higher sea levels during interglacial periods isolated these regions and warmer temperatures restricted temperate taxa to disjunct refuges. However, palaeovegetation data from east Asia show that temperate forests were considerably less extensive than today during the Last Glacial Maximum, calling into question the coalescence of tree populations required by the hypothesis of Qian and Ricklefs.     

A high-velocity black hole on a Galactic-halo orbit in the solar neighbourhood

Only a few of the dozen or so known stellar-mass black holes have been observed away from the plane of the Galaxy. Those few could have been ejected from the plane as a result of a 'kick' received during a supernova explosion, or they could be remnants of the population of massive stars formed in the early stages of evolution of the Galaxy. Determining their orbital motion should help to distinguish between these options. Here we report the transverse motion (in the plane of the sky) for the black-hole X-ray nova XTE J1118+480 (refs 2, 3, 4, 5), from which we derive a large space velocity. This X-ray binary system has an eccentric orbit around the Galactic Centre, like most objects in the halo of the Galaxy, such as ancient stars and globular clusters. The properties of the system suggest that its age is comparable to or greater than the age of the Galactic disk. Only an extraordinary 'kick' from a supernova could have launched the black hole into an orbit like this from a birthplace in the disk of the Galaxy.