Assembly of microarrays for genome-wide measurement of DNA copy number.

We have assembled arrays of approximately 2,400 BAC clones for measurement of DNA copy number across the human genome. The arrays provide precise measurement (s.d. of log2 ratios=0.05-0.10) in cell lines and clinical material, so that we can reliably detect and quantify high-level amplifications and single-copy alterations in diploid, polyploid and heterogeneous backgrounds.     

The association of GRB 060218 with a supernova and the evolution of the shock wave

Although the link between long gamma-ray bursts (GRBs) and supernovae has been established, hitherto there have been no observations of the beginning of a supernova explosion and its intimate link to a GRB. In particular, we do not know how the jet that defines a gamma-ray burst emerges from the star's surface, nor how a GRB progenitor explodes. Here we report observations of the relatively nearby GRB 060218 (ref. 5) and its connection to supernova SN 2006aj (ref. 6). In addition to the classical non-thermal emission, GRB 060218 shows a thermal component in its X-ray spectrum, which cools and shifts into the optical/ultraviolet band as time passes. We interpret these features as arising from the break-out of a shock wave driven by a mildly relativistic shell into the dense wind surrounding the progenitor. We have caught a supernova in the act of exploding, directly observing the shock break-out, which indicates that the GRB progenitor was a Wolf-Rayet star.     

Dynein mutations impair autophagic clearance of aggregate-prone proteins

Mutations that affect the dynein motor machinery are sufficient to cause motor neuron disease. It is not known why there are aggregates or inclusions in affected tissues in mice with such mutations and in most forms of human motor neuron disease. Here we identify a new mechanism of inclusion formation by showing that decreased dynein function impairs autophagic clearance of aggregate-prone proteins. We show that mutations of the dynein machinery enhanced the toxicity of the mutation that causes Huntington disease in fly and mouse models. Furthermore, loss of dynein function resulted in premature aggregate formation by mutant huntingtin and increased levels of the autophagosome marker LC3-II in both cell culture and mouse models, compatible with impaired autophagosome-lysosome fusion.     

Stochastic and genetic factors influence tissue-specific decline in ageing C. elegans

The nematode Caenorhabditis elegans is an important model for studying the genetics of ageing, with over 50 life-extension mutations known so far. However, little is known about the pathobiology of ageing in this species, limiting attempts to connect genotype with senescent phenotype. Using ultrastructural analysis and visualization of specific cell types with green fluorescent protein, we examined cell integrity in different tissues as the animal ages. We report remarkable preservation of the nervous system, even in advanced old age, in contrast to a gradual, progressive deterioration of muscle, resembling human sarcopenia. The age-1(hx546) mutation, which extends lifespan by 60-100%, delayed some, but not all, cellular biomarkers of ageing. Strikingly, we found strong evidence that stochastic as well as genetic factors are significant in C. elegans ageing, with extensive variability both among same-age animals and between cells of the same type within individuals.     

Direct detection of variable tropospheric clouds near Titan's south pole

Atmospheric conditions on Saturn's largest satellite, Titan, allow the possibility that it could possess a methane condensation and precipitation cycle with many similarities to Earth's hydrological cycle. Detailed imaging studies of Titan have hitherto shown no direct evidence for tropospheric condensation clouds, although there has been indirect spectroscopic evidence for transient clouds. Here we report images and spectra of Titan that show clearly transient clouds, concentrated near the south pole, which is currently near the point of maximum solar heating. The discovery of these clouds demonstrates the existence of condensation and localized moist convection in Titan's atmosphere. Their location suggests that methane cloud formation is controlled seasonally by small variations in surface temperature, and that the clouds will move from the south to the north pole on a 15-year timescale.     

The flux of small near-Earth objects colliding with the Earth

Asteroids with diameters smaller than approximately 50-100 m that collide with the Earth usually do not hit the ground as a single body; rather, they detonate in the atmosphere. These small objects can still cause considerable damage, such as occurred near Tunguska, Siberia, in 1908. The flux of small bodies is poorly constrained, however, in part because ground-based observational searches pursue strategies that lead them preferentially to find larger objects. A Tunguska-class event-the energy of which we take to be equivalent to 10 megatons of TNT-was previously estimated to occur every 200-300 years, with the largest annual airburst calculated to be approximately 20 kilotons (kton) TNT equivalent (ref. 4). Here we report satellite records of bolide detonations in the atmosphere over the past 8.5 years. We find that the flux of objects in the 1-10-m size range has the same power-law distribution as bodies with diameters >50 m. From this we estimate that the Earth is hit on average annually by an object with approximately 5 kton equivalent energy, and that Tunguska-like events occur about once every 1,000 years.     

The genome sequence of Schizosaccharomyces pombe

We have sequenced and annotated the genome of fission yeast (Schizosaccharomyces pombe), which contains the smallest number of protein-coding genes yet recorded for a eukaryote: 4,824. The centromeres are between 35 and 110 kilobases (kb) and contain related repeats including a highly conserved 1.8-kb element. Regions upstream of genes are longer than in budding yeast (Saccharomyces cerevisiae), possibly reflecting more-extended control regions. Some 43% of the genes contain introns, of which there are 4,730. Fifty genes have significant similarity with human disease genes; half of these are cancer related. We identify highly conserved genes important for eukaryotic cell organization including those required for the cytoskeleton, compartmentation, cell-cycle control, proteolysis, protein phosphorylation and RNA splicing. These genes may have originated with the appearance of eukaryotic life. Few similarly conserved genes that are important for multicellular organization were identified, suggesting that the transition from prokaryotes to eukaryotes required more new genes than did the transition from unicellular to multicellular organization.     

myo-Inositol polyphosphate may be a messenger for visual excitation in Limulus photoreceptors

Photoreceptor excitation begins with the absorption of a photon by rhodopsin and proceeds through an unknown sequence of steps that leads to changes in specific ionic conductances. These conductance changes produce the receptor potential. It has been proposed that hydrolysis of phosphoinositides is involved in the control of a variety of physiological processes. Recent studies have implicated inositol 1,4,5-trisphosphate as an intracellular messenger in the cascade mediating hormone-stimulated secretion. We propose that one of the steps in the excitatory cascade in Limulus ventral photoreceptors may be an increase in intracellular concentration of myo-inositol polyphosphates, derived from hydrolysis of the membrane component phosphatidylinositol bisphosphate by a phospholipase. Here we present biochemical and electrophysiological evidence that an inositol polyphosphate may be an intracellular messenger in the cascade mediating excitation, based on the following criteria: the cells possess the synthetic and degradative metabolism for the messenger; the natural stimulus leads to a change in the concentration of the messenger within the cells; and intracellular injection of exogenous messenger mimics naturally occurring electrophysiological events.     

Electro-optical shift

Zusammenfassung Erzeugt man in einem flüssigen Dielektrikum, wie wasserfreiem Äthanol, Schwefelkohlenstoff, p-Tolylazetat oder Nitrobenzol, zwischen speziell gestalteten Elektroden ein elektrisches Feld von etwa 10000 V/cm, so wird ein Lichtstrahl, der die im Feld befindlichen Teile der Flüssigkeit durchsetzt, gekrümmt. Die Ablenkung des Strahls aus der geraden Richtung beträgt in manchen Fällen 1°.