Analysis of the DNA sequence and duplication history of human chromosome 15

Here we present a finished sequence of human chromosome 15, together with a high-quality gene catalogue. As chromosome 15 is one of seven human chromosomes with a high rate of segmental duplication, we have carried out a detailed analysis of the duplication structure of the chromosome. Segmental duplications in chromosome 15 are largely clustered in two regions, on proximal and distal 15q; the proximal region is notable because recombination among the segmental duplications can result in deletions causing Prader-Willi and Angelman syndromes. Sequence analysis shows that the proximal and distal regions of 15q share extensive ancient similarity. Using a simple approach, we have been able to reconstruct many of the events by which the current duplication structure arose. We find that most of the intrachromosomal duplications seem to share a common ancestry. Finally, we demonstrate that some remaining gaps in the genome sequence are probably due to structural polymorphisms between haplotypes; this may explain a significant fraction of the gaps remaining in the human genome.     

Planar cell polarity signalling couples cell division and morphogenesis during neurulation

Environmental and genetic aberrations lead to neural tube closure defects (NTDs) in 1 out of every 1,000 births. Mouse and frog models for these birth defects have indicated that Van Gogh-like 2 (Vangl2, also known as Strabismus) and other components of planar cell polarity (PCP) signalling might control neurulation by promoting the convergence of neural progenitors to the midline. Here we show a novel role for PCP signalling during neurulation in zebrafish. We demonstrate that non-canonical Wnt/PCP signalling polarizes neural progenitors along the anteroposterior axis. This polarity is transiently lost during cell division in the neural keel but is re-established as daughter cells reintegrate into the neuroepithelium. Loss of zebrafish Vangl2 (in trilobite mutants) abolishes the polarization of neural keel cells, disrupts re-intercalation of daughter cells into the neuroepithelium, and results in ectopic neural progenitor accumulations and NTDs. Remarkably, blocking cell division leads to rescue of trilobite neural tube morphogenesis despite persistent defects in convergence and extension. These results reveal a function for PCP signalling in coupling cell division and morphogenesis at neurulation and indicate a previously unrecognized mechanism that might underlie NTDs.     

A photometric redshift of z = 6.39 +/- 0.12 for GRB 050904

Gamma-ray bursts (GRBs) and their afterglows are the most brilliant transient events in the Universe. Both the bursts themselves and their afterglows have been predicted to be visible out to redshifts of z approximately 20, and therefore to be powerful probes of the early Universe. The burst GRB 000131, at z = 4.50, was hitherto the most distant such event identified. Here we report the discovery of the bright near-infrared afterglow of GRB 050904 (ref. 4). From our measurements of the near-infrared afterglow, and our failure to detect the optical afterglow, we determine the photometric redshift of the burst to be z = 6.39 - 0.12 + 0.11 (refs 5-7). Subsequently, it was measured spectroscopically to be z = 6.29 +/- 0.01, in agreement with our photometric estimate. These results demonstrate that GRBs can be used to trace the star formation, metallicity, and reionization histories of the early Universe.     

The PerR transcription factor senses H2O2 by metal-catalysed histidine oxidation

The sensing of reactive oxygen species is essential for cellular responses to oxidative stress. The sensing of peroxides is typically mediated by redox-active cysteines in sensors such as the bacterial OxyR, OhrR, and Hsp33 proteins. Bacillus subtilis PerR is the prototype for a widespread family of metal-dependent peroxide sensors that regulate inducible peroxide-defence genes. Here we show that PerR senses peroxides by metal-catalysed oxidation. PerR contains two metal-binding sites: a structural Zn2+ site and a regulatory divalent metal ion site that preferentially binds Fe2+ or Mn2+ (ref. 5). Protein oxidation, catalysed by a bound ferrous ion, leads to the rapid and direct incorporation of one oxygen atom into histidine 37 (H37) or H91, two of the residues that coordinate the bound Fe2+. This mechanism accounts for the ability of PerR to sense low levels of hydrogen peroxide in vivo. The reduction of hydrogen peroxide by metal ions to generate highly reactive hydroxyl radicals underlies the genotoxic effects of peroxides, and has been shown to contribute to enzyme inactivation, but has not previously been shown to provide a regulatory mechanism for peroxide sensing.     

Editing-defective tRNA synthetase causes protein misfolding and neurodegeneration

Misfolded proteins are associated with several pathological conditions including neurodegeneration. Although some of these abnormally folded proteins result from mutations in genes encoding disease-associated proteins (for example, repeat-expansion diseases), more general mechanisms that lead to misfolded proteins in neurons remain largely unknown. Here we demonstrate that low levels of mischarged transfer RNAs (tRNAs) can lead to an intracellular accumulation of misfolded proteins in neurons. These accumulations are accompanied by upregulation of cytoplasmic protein chaperones and by induction of the unfolded protein response. We report that the mouse sticky mutation, which causes cerebellar Purkinje cell loss and ataxia, is a missense mutation in the editing domain of the alanyl-tRNA synthetase gene that compromises the proofreading activity of this enzyme during aminoacylation of tRNAs. These findings demonstrate that disruption of translational fidelity in terminally differentiated neurons leads to the accumulation of misfolded proteins and cell death, and provide a novel mechanism underlying neurodegeneration.     

Metallic transport in polyaniline

Despite nearly three decades of materials development, the transport properties in the 'metallic state' of the so-called conducting polymers are still not typical of conventional metals. The hallmark of metallic resistivity--a monotonic decrease in resistivity with temperature--has not been obtained at temperatures over the full range below room temperature; and a frequency dependent conductivity, sigma(omega), typical of metals has also not been observed. In contrast, the low-temperature behaviour of 'metallic' polymers has, in all previous cases, exhibited an increase in resistivity as temperature is further decreased, as a result of disorder-induced localization of the charge carriers. This disorder-induced localization also changes the infrared response such that sigma(omega) deviates from the prediction of Drude theory. Here we report classic metallic transport data obtained from truly metallic polymers. With polyaniline samples prepared using self-stabilized dispersion polymerization, we find that for samples having room-temperature conductivities in excess of 1,000 S cm(-1), the resistivity decreases monotonically as the temperature is lowered down to 5 K, and that the infrared spectra are characteristic of the conventional Drude model even at the lowest frequencies measured.     

A radioimmunoassay for dopamine-β-hydroxylase using a glass-bound antibody

Résumé Les auteurs décrivent une méthode radioimmunologique de dosage de la DH utilisant un anticorps lié de façon covalente à des billes de verre. La technique a été appliquée à la mesure de la DH dans les surrénales et différentes régions du cerveau de buf. Les principaux avantages de cette méthode sont sa relative facilité d'emploi, sa précision et sa haute spécificité.

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This work was supported by USPHS Grants Nos. MH-02717, NS-06801 and CA-02071 and NSF Grant No. GB-27603.Acknowledgements: The authors wish to express their appreciation for the technical assistance of Susan Kadner and William P. Vann.     

A Study of a Stand- Alone Type Variable Speed Wind Tur bine System with Synchronous Generator

Most recently produced wind generators use variable-speed systems for high-efficiency operation and low mechanical stress.In this study of a variable-speed standalone system that uses a synchronous machine,a power converter for the system was developed and tested.The maximum power points were approximated in a line according to the wind speed changes,and the linear approximation MPPT algorithm was used to determine the duty ratio that corresponds to the intersection point of the observed power and linearized line using the power generated from the generator at a point.With the fabricated converter,it was verified that the voltage,current and theta were normal with the varied load current.