Proteorhodopsin in the ubiquitous marine bacterium SAR11

Proteorhodopsins are light-dependent proton pumps that are predicted to have an important role in the ecology of the oceans by supplying energy for microbial metabolism. Proteorhodopsin genes were first discovered through the cloning and sequencing of large genomic DNA fragments from seawater. They were later shown to be widely distributed, phylogenetically diverse, and active in the oceans. Proteorhodopsin genes have not been found in cultured bacteria, and on the basis of environmental sequence data, it has not yet been possible to reconstruct the genomes of uncultured bacterial strains that have proteorhodopsin genes. Although the metabolic effect of proteorhodopsins is uncertain, they are thought to function in cells for which the primary mode of metabolism is the heterotrophic assimilation of dissolved organic carbon. Here we report that SAR11 strain HTCC1062 ('Pelagibacter ubique'), the first cultivated member of the extraordinarily abundant SAR11 clade, expresses a proteorhodopsin gene when cultured in autoclaved seawater and in its natural environment, the ocean. The Pelagibacter proteorhodopsin functions as a light-dependent proton pump. The gene is expressed by cells grown in either diurnal light or in darkness, and there is no difference between the growth rates or cell yields of cultures grown in light or darkness.     

Relationship of prodigiosin condensing enzyme activity to the biosynthesis of prodigiosin and its precursors inSerratia marcescens

Summary Prodigiosin condensing enzyme (PCE) activities were present inSerratia marcescens wild type 08, mutants OF, WF and 9-3-3. Their specific activities exhibited different maxima and at different times during the late log phase or the early stationary phase of cell growth. The levels of prodigiosin and its precursors also showed a significant increase at this period. The results support that prodigiosin and/or its precursors are secondary metabolites. The ubiquity of the PCE activity in mutants deficient in prodigiosin biosynthesis suggest that this particular enzyme may also be present in non-pigmented clinical isolates.     

Three-dimensional binary superlattices of magnetic nanocrystals and semiconductor quantum dots

Recent advances in strategies for synthesizing nanoparticles--such as semiconductor quantum dots, magnets and noble-metal clusters--have enabled the precise control of composition, size, shape, crystal structure, and surface chemistry. The distinct properties of the resulting nanometre-scale building blocks can be harnessed in assemblies with new collective properties, which can be further engineered by controlling interparticle spacing and by material processing. Our study is motivated by the emerging concept of metamaterials-materials with properties arising from the controlled interaction of the different nanocrystals in an assembly. Previous multi-component nanocrystal assemblies have usually resulted in amorphous or short-range-ordered materials because of non-directional forces or insufficient mobility during assembly. Here we report the self-assembly of PbSe semiconductor quantum dots and Fe2O3 magnetic nanocrystals into precisely ordered three-dimensional superlattices. The use of specific size ratios directs the assembly of the magnetic and semiconducting nanoparticles into AB13 or AB2 superlattices with potentially tunable optical and magnetic properties. This synthesis concept could ultimately enable the fine-tuning of material responses to magnetic, electrical, optical and mechanical stimuli.     

Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab

HER2 (also known as Neu, ErbB2) is a member of the epidermal growth factor receptor (EGFR; also known as ErbB) family of receptor tyrosine kinases, which in humans includes HER1 (EGFR, ERBB1), HER2, HER3 (ERBB3) and HER4 (ERBB4). ErbB receptors are essential mediators of cell proliferation and differentiation in the developing embryo and in adult tissues, and their inappropriate activation is associated with the development and severity of many cancers. Overexpression of HER2 is found in 20-30% of human breast cancers, and correlates with more aggressive tumours and a poorer prognosis. Anticancer therapies targeting ErbB receptors have shown promise, and a monoclonal antibody against HER2, Herceptin (also known as trastuzumab), is currently in use as a treatment for breast cancer. Here we report crystal structures of the entire extracellular regions of rat HER2 at 2.4 A and human HER2 complexed with the Herceptin antigen-binding fragment (Fab) at 2.5 A. These structures reveal a fixed conformation for HER2 that resembles a ligand-activated state, and show HER2 poised to interact with other ErbB receptors in the absence of direct ligand binding. Herceptin binds to the juxtamembrane region of HER2, identifying this site as a target for anticancer therapies.     

CTCF-binding sites flank CTG/CAG repeats and form a methylation-sensitive insulator at the DM1 locus

An expansion of a CTG repeat at the DM1 locus causes myotonic dystrophy (DM) by altering the expression of the two adjacent genes, DMPK and SIX5, and through a toxic effect of the repeat-containing RNA. Here we identify two CTCF-binding sites that flank the CTG repeat and form an insulator element between DMPK and SIX5. Methylation of these sites prevents binding of CTCF, indicating that the DM1 locus methylation in congenital DM would disrupt insulator function. Furthermore, CTCF-binding sites are associated with CTG/CAG repeats at several other loci. We suggest a general role for CTG/CAG repeats as components of insulator elements at multiple sites in the human genome.     

Essential role of the mitochondrial apoptosis-inducing factor in programmed cell death

Programmed cell death is a fundamental requirement for embryogenesis, organ metamorphosis and tissue homeostasis. In mammals, release of mitochondrial cytochrome c leads to the cytosolic assembly of the apoptosome-a caspase activation complex involving Apaf1 and caspase-9 that induces hallmarks of apoptosis. There are, however, mitochondrially regulated cell death pathways that are independent of Apaf1/caspase-9. We have previously cloned a molecule associated with programmed cell death called apoptosis-inducing factor (AIF). Like cytochrome c, AIF is localized to mitochondria and released in response to death stimuli. Here we show that genetic inactivation of AIF renders embryonic stem cells resistant to cell death after serum deprivation. Moreover, AIF is essential for programmed cell death during cavitation of embryoid bodies-the very first wave of cell death indispensable for mouse morphogenesis. AIF-dependent cell death displays structural features of apoptosis, and can be genetically uncoupled from Apaf1 and caspase-9 expression. Our data provide genetic evidence for a caspase-independent pathway of programmed cell death that controls early morphogenesis.     

N-ethylmaleimide antagonizes stress-induced gastric ulcers in rats

Summary N-ethylmaleimide (NEM) 10 or 25 mg/kg b.wt, given s.c. 20 min beforehand, dose-dependently and significantly antagonizes the severity of gastric glandular ulcers produced by restraint at 4°C (stress) for 2 h. These findings suggest that reduced activity of endogenous nonprotein sulfhydryl substances in gastric tissue does not worsen stress-induced ulceration in rat stomachs, unlike the deleterious effect its depletion is claimed to have on ethanol-evoked gastric mucosal damage. Thus, decreased SH activity appears not to play a role in the aetiology of mucosal ulcers due to stress.     

Variance intervention

Variance intervention is a simple state-space approach to handling sharp discontinuities of level or slope in the states or parameters of models for non-stationary time-series. It derives from earlier procedures used in the 1960s for the design of self-adaptive, state variable feedback control systems. In the alternative state-space forecasting context considered in the present paper, it is particularly useful when applied to structural time series models. The paper compares the variance intervention procedure with the related ‘subjective intervention’ approach proposed by West and Harrison in a recent issue of the Journal of Forecasting, and demonstrates it efficacy by application to various time-series data, including those used by West and Harrison.     

Large-scale synthesis of a silicon photonic crystal with a complete three-dimensional bandgap near 1.5 micrometres

Photonic technology, using light instead of electrons as the information carrier, is increasingly replacing electronics in communication and information management systems. Microscopic light manipulation, for this purpose, is achievable through photonic bandgap materials, a special class of photonic crystals in which three-dimensional, periodic dielectric constant variations controllably prohibit electromagnetic propagation throughout a specified frequency band. This can result in the localization of photons, thus providing a mechanism for controlling and inhibiting spontaneous light emission that can be exploited for photonic device fabrication. In fact, carefully engineered line defects could act as waveguides connecting photonic devices in all-optical microchips, and infiltration of the photonic material with suitable liquid crystals might produce photonic bandgap structures (and hence light-flow patterns) fully tunable by an externally applied voltage. However, the realization of this technology requires a strategy for the efficient synthesis of high-quality, large-scale photonic crystals with photonic bandgaps at micrometre and sub-micrometre wavelengths, and with rationally designed line and point defects for optical circuitry. Here we describe single crystals of silicon inverse opal with a complete three-dimensional photonic bandgap centred on 1.46 microm, produced by growing silicon inside the voids of an opal template of dose-packed silica spheres that are connected by small 'necks' formed during sintering, followed by removal of the silica template. The synthesis method is simple and inexpensive, yielding photonic crystals of pure silicon that are easily integrated with existing silicon-based microelectronics.