The landing of the NEAR-Shoemaker spacecraft on asteroid 433 Eros

The NEAR-Shoemaker spacecraft was designed to provide a comprehensive characterization of the S-type asteroid 433 Eros (refs 1,2,3), an irregularly shaped body with approximate dimensions of 34 x 13 x 13 km. Following the completion of its year-long investigation, the mission was terminated with a controlled descent to its surface, in order to provide extremely high resolution images. Here we report the results of the descent on 12 February 2001, during which 70 images were obtained. The landing area is marked by a paucity of small craters and an abundance of 'ejecta blocks'. The properties and distribution of ejecta blocks are discussed in a companion paper. The last sequence of images reveals a transition from the blocky surface to a smooth area, which we interpret as a 'pond'. Properties of the 'ponds' are discussed in a second companion paper. The closest image, from an altitude of 129 m, shows the interior of a 100-m-diameter crater at 1-cm resolution.     

Microdomain patterns from directional eutectic solidification and epitaxy

Creating a regular surface pattern on the nanometre scale is important for many technological applications, such as the periodic arrays constructed by optical microlithography that are used as separation media in electrophoresis, and island structures used for high-density magnetic recording devices. Block copolymer patterns can also be used for lithography on length scales below 30 nanometres (refs 3-5). But for such polymers to prove useful for thin-film technologies, chemically patterned surfaces need to be made substantially defect-free over large areas, and with tailored domain orientation and periodicity. So far, control over domain orientation has been achieved by several routes, using electric fields, temperature gradients, patterned substrates and neutral confining surfaces. Here we describe an extremely fast process that leads the formation of two-dimensional periodic thin films having large area and uniform thickness, and which possess vertically aligned cylindrical domains each containing precisely one crystalline lamella. The process involves rapid solidification of a semicrystalline block copolymer from a crystallizable solvent between glass substrates using directional solidification and epitaxy. The film is both chemically and structurally periodic, thereby providing new opportunities for more selective and versatile nanopatterned surfaces.     

The effects of a heterologous antibody against a crude lipoprotein lipase fraction in mice]

The antigens contained in a crude lipoprotein-lipase fraction from the Rabbit adipose tissue have no effect on Mice, even after daily injections for several months. But they induce an immune reaction in Sheep, allowing one to produce several immune sera with a high physiological activity, without any specific barrier between Rabbit and Mouse. After total absorption of these immune sera by normal Rabbit serum, the remaining antibodies have an activity against esterasic lipoproteins. Small doses of these antibodies induce in Mice marked hyperplastic and degenerative reactions of the adipose tissue and an extensive lysis of the pancreas. A correlative high lymphocytic activation, producing B and T immunoblasts, is induced.     

The monamycins,a new family of cyclodepsipeptide antibiotics

Zusammenfassung Die Analyse von Monamycin, einem Antibiotika-Komplex, führte zur Identifizierung der 15 Cyclohexadepsipeptidkomponenten. Für Monamycin D₁ wurde Strukturformel V abgeleitet.     

The netrin receptor UNC5B mediates guidance events controlling morphogenesis of the vascular system

Blood vessels and nerves are complex, branched structures that share a high degree of anatomical similarity. Guidance of vessels and nerves has to be exquisitely regulated to ensure proper wiring of both systems. Several regulators of axon guidance have been identified and some of these are also expressed in endothelial cells; however, the extent to which their guidance functions are conserved in the vascular system is still incompletely understood. We show here that the repulsive netrin receptor UNC5B is expressed by endothelial tip cells of the vascular system. Disruption of the Unc5b gene in mice, or of Unc5b or netrin-1a in zebrafish, leads to aberrant extension of endothelial tip cell filopodia, excessive vessel branching and abnormal navigation. Netrin-1 causes endothelial filopodial retraction, but only when UNC5B is present. Thus, UNC5B functions as a repulsive netrin receptor in endothelial cells controlling morphogenesis of the vascular system.     

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.     

Genetic variation in DLG5 is associated with inflammatory bowel disease

Crohn disease and ulcerative colitis are two subphenotypes of inflammatory bowel disease (IBD), a complex disorder resulting from gene-environment interaction. We refined our previously defined linkage region for IBD on chromosome 10q23 and used positional cloning to identify genetic variants in DLG5 associated with IBD. DLG5 encodes a scaffolding protein involved in the maintenance of epithelial integrity. We identified two distinct haplotypes with a replicable distortion in transmission (P = 0.000023 and P = 0.004 for association with IBD, P = 0.00012 and P = 0.04 for association with Crohn disease). One of the risk-associated DLG5 haplotypes is distinguished from the common haplotype by a nonsynonymous single-nucleotide polymorphism 113G-->A, resulting in the amino acid substitution R30Q in the DUF622 domain of DLG5. This mutation probably impedes scaffolding of DLG5. We stratified the study sample according to the presence of risk-associated CARD15 variants to study potential gene-gene interaction. We found a significant difference in association of the 113A DLG5 variant with Crohn disease in affected individuals carrying the risk-associated CARD15 alleles versus those carrying non-risk-associated CARD15 alleles. This is suggestive of a complex pattern of gene-gene interaction between DLG5 and CARD15, reflecting the complex nature of polygenic diseases. Further functional studies will evaluate the biological significance of DLG5 variants.     

'Racial' differences in genetic effects for complex diseases

'Racial' differences are frequently debated in clinical, epidemiological and molecular research and beyond. In particular, there is considerable controversy regarding the existence and importance of 'racial' differences in genetic effects for complex diseases influenced by a large number of genes. An important question is whether ancestry influences the impact of each gene variant on the disease risk. Here, we addressed this question by examining the genetic effects for 43 validated gene-disease associations across 697 study populations of various descents. The frequencies of the genetic marker of interest in the control populations often (58%) showed large heterogeneity (statistical variability) between 'races'. Conversely, we saw large heterogeneity in the genetic effects (odds ratios) between 'races' in only 14% of cases. Genetic markers for proposed gene-disease associations vary in frequency across populations, but their biological impact on the risk for common diseases may usually be consistent across traditional 'racial' boundaries.     

Climate (communication arising): impact of land-use change on climate

Urbanization and other changes in land use have an impact on surface-air temperatures. Kalnay and Cai report that the observed surface-temperature trend in part of the United States exceeds the trend in the NCEP/NCAR 50-year reanalysis (NNR) and conclude that changes in land use account for the difference (0.035 degrees C per decade according to their corrected values). Although land-use change may explain some of this discrepancy, the authors do not quantify the impact of the many changes in observational practice that occurred during the analysis period. Our findings indicate that these 'non-climatic' changes have a systematic effect that overwhelms the reported difference in trends and therefore calls Kalnay and Cai's central conclusion into question.