Two classes of metabolites fromTheonella swinhoei are localized in distinct populations of bacterial symbionts

The marine spongeTheonella swinhoei (lithistid Family Theonellidae, Order Astrophorida) has yielded many important, bioactive natural products, most of which share structural features with bacterial natural products. The presence of microbial symbionts inT. swinhoei has been reported, and it was originally suggested that the cytotoxic macrolide swinholide A and many of the bioactive cyclic peptides fromT. swinhoei were all produced by symbiotic cyanobacteria. By transmission electron microscopy, we found four distinct cell populations to be consistently present inT. swinhoei: eukaryotic sponge cells, unicellular heterotrophic bacteria, unicellular cyanobacteria and filamentous heterotrophic bacteria. Purification and chemical analyses of each cell type showed the macrolide swinholide A to be limited to the mixed population of unicellular heterotrophic bacteria, and an anti-fungal cyclic peptide occurred only in the filamentous heterotrophic bacteria. Contrary to prior speculation, no major metabolites were located in the cyanobacteria or sponge cells.     

The DNA sequence and analysis of human chromosome 13

Chromosome 13 is the largest acrocentric human chromosome. It carries genes involved in cancer including the breast cancer type 2 (BRCA2) and retinoblastoma (RB1) genes, is frequently rearranged in B-cell chronic lymphocytic leukaemia, and contains the DAOA locus associated with bipolar disorder and schizophrenia. We describe completion and analysis of 95.5 megabases (Mb) of sequence from chromosome 13, which contains 633 genes and 296 pseudogenes. We estimate that more than 95.4% of the protein-coding genes of this chromosome have been identified, on the basis of comparison with other vertebrate genome sequences. Additionally, 105 putative non-coding RNA genes were found. Chromosome 13 has one of the lowest gene densities (6.5 genes per Mb) among human chromosomes, and contains a central region of 38 Mb where the gene density drops to only 3.1 genes per Mb.     

Limb-girdle muscular dystrophy type 2G is caused by mutations in the gene encoding the sarcomeric protein telethonin

Autosomal recessive limb-girdle muscular dystrophies (AR LGMDs) are a genetically heterogeneous group of disorders that affect mainly the proximal musculature. There are eight genetically distinct forms of AR LGMD, LGMD 2A-H (refs 2-10), and the genetic lesions underlying these forms, except for LGMD 2G and 2H, have been identified. LGMD 2A and LGMD 2B are caused by mutations in the genes encoding calpain 3 (ref. 11) and dysferlin, respectively, and are usually associated with a mild phenotype. Mutations in the genes encoding gamma-(ref. 14), alpha-(ref. 5), beta-(refs 6,7) and delta (ref. 15)-sarcoglycans are responsible for LGMD 2C to 2F, respectively. Sarcoglycans, together with sarcospan, dystroglycans, syntrophins and dystrobrevin, constitute the dystrophin-glycoprotein complex (DGC). Patients with LGMD 2C-F predominantly have a severe clinical course. The LGMD 2G locus maps to a 3-cM interval in 17q11-12 in two Brazilian families with a relatively mild form of AR LGMD (ref. 9). To positionally clone the LGMD 2G gene, we constructed a physical map of the 17q11-12 region and refined its localization to an interval of 1.2 Mb. The gene encoding telethonin, a sarcomeric protein, lies within this candidate region. We have found that mutations in the telethonin gene cause LGMD 2G, identifying a new molecular mechanism for AR LGMD.     

Luffolide,a novel anti-inflammatory terpene from the spongeLuffariella sp.

Summary Luffolide (4) is a minor metabolite of the spongeLuffariella sp. from Palau. The structure of luffolide was determined by single crystal X-ray analysis. Luffolide is relatively unstable and undergoes a complex cyclization reaction to give the hexacyclic products5 and6. Luffolide (4) has some of the anti-inflammatory properties of manoalide (1): this may help to define the chemical reaction between manoalide (1) and phospholipase A₂.All crystallographic calculations were done on a PRIME 9950 computer operated by the Cornell Chemistry Computing Facility. Principal programs employed were: FOBS, a data reduction program by G.D. Van Duyne, Cornell University, 1987; MULTAN 80, and RANTAN 80, systems of computer programs for the automatic solution of crystal structures from X-ray diffraction data (locally modified to perform all Fourier calculations including Patterson syntheses) written by P. Main, S. E. Hull, L. Lessinger, G. Germain, J. P. Declercq and M. M. Woolfson, University of York, England, 1980 BDLS, an, anisotropic block diagonal least squares refinement written by K. Hirotsu, E. Arnold, and G. D. Van Duyne, Cornell University, 1987; PLUTO 78, a locally modified crystallographic illustration program by W. D. S. Motherwell, Cambridge Crystallographic Data Centre, 1978; and BOND, a program to calculate molecular parameters and prepare tables written by K. Hirotsu and G. Van Duyne, Cornell University, 1985.Acknowledgment. We thank the Government of the Republic of Palau for a scientific research permit. We thank Dr Klaus Rützler, Smithsonian Institution, Washington, D.C. for identifying the sponge and Mary Kay Harper for performing additional bioassays. This research was supported by grants from the Sea Grant College Programs of California [Projects R/MP-30 to DJF) and R/MP-31 (to RSJ)] and New York (to JC) and the National Institutes of Health (CA 24487 to JC).     

Slip on 'weak' faults by the rotation of regional stress in the fracture damage zone

Slip on unfavourably oriented faults with respect to a remotely applied stress is well documented and implies that faults such as the San Andreas fault and low-angle normal faults are weak when compared to laboratory-measured frictional strength. If high pore pressure within fault zones is the cause of such weakness, then stress reorientation within or close to a fault is necessary to allow sufficient fault weakening without the occurrence of hydrofracture. From field observations of a major tectonic fault, and using laboratory experiments and numerical modelling, here we show that stress rotation occurs within the fractured damage zone surrounding faults. In particular, we find that stress rotation is considerable for unfavourably oriented 'weak' faults. In the 'weak' fault case, the damage-induced change in elastic properties provides the necessary stress rotation to allow high pore pressure faulting without inducing hydrofracture.     

Transient radio bursts from rotating neutron stars

The radio sky is relatively unexplored for transient signals, although the potential of radio-transient searches is high. This was demonstrated recently by the discovery of a previously unknown type of source, varying on timescales of minutes to hours. Here we report a search for radio sources that vary on much shorter timescales. We found eleven objects characterized by single, dispersed bursts having durations between 2 and 30 ms. The average time intervals between bursts range from 4 min to 3 h with radio emission typically detectable for <1 s per day. From an analysis of the burst arrival times, we have identified periodicities in the range 0.4-7 s for ten of the eleven sources, suggesting origins in rotating neutron stars. Despite the small number of sources detected at present, their ephemeral nature implies a total Galactic population significantly exceeding that of the regularly pulsing radio pulsars. Five of the ten sources have periods >4 s, and the rate of change of the pulse period has been measured for three of them; for one source, we have inferred a high magnetic field strength of 5 x 10(13) G. This suggests that the new population is related to other classes of isolated neutron stars observed at X-ray and gamma-ray wavelengths.     

Investigation of coupled cobalt–silver nanoparticle system by plan view TEM

We present a transmission electron microscopy (TEM) investigation of a coupled cobalt and silver nanoparticle system. A plan view in situ lift-out method for preparing samples for TEM using the focused ion beam (FIB) microscope was used. This technique is used to prepare high quality TEM samples with site specificity in a short time and with a high success rate. We demonstrate the ability of the plan view sample preparation technique to provide information about an ordered system of nanoparticles which could not be observed using standard FIB cross sectioning of the sample. High resolution TEM and energy dispersive X-ray spectroscopy mapping of both cross sectional and plan view samples are presented, clearly showing the significant benefit of plan view TEM analysis for certain samples