The gene mutated in ataxia-ocular apraxia 1 encodes the new HIT/Zn-finger protein aprataxin

The newly recognized ataxia-ocular apraxia 1 (AOA1; MIM 208920) is the most frequent cause of autosomal recessive ataxia in Japan and is second only to Friedreich ataxia in Portugal. It shares several neurological features with ataxia-telangiectasia, including early onset ataxia, oculomotor apraxia and cerebellar atrophy, but does not share its extraneurological features (immune deficiency, chromosomal instability and hypersensitivity to X-rays). AOA1 is also characterized by axonal motor neuropathy and the later decrease of serum albumin levels and elevation of total cholesterol. We have identified the gene causing AOA1 and the major Portuguese and Japanese mutations. This gene encodes a new, ubiquitously expressed protein that we named aprataxin. This protein is composed of three domains that share distant homology with the amino-terminal domain of polynucleotide kinase 3'- phosphatase (PNKP), with histidine-triad (HIT) proteins and with DNA-binding C2H2 zinc-finger proteins, respectively. PNKP is involved in DNA single-strand break repair (SSBR) following exposure to ionizing radiation and reactive oxygen species. Fragile-HIT proteins (FHIT) cleave diadenosine tetraphosphate, which is potentially produced during activation of the SSBR complex. The results suggest that aprataxin is a nuclear protein with a role in DNA repair reminiscent of the function of the protein defective in ataxia-telangiectasia, but that would cause a phenotype restricted to neurological signs when mutant.     

An efficient room-temperature silicon-based light-emitting diode

There is an urgent requirement for an optical emitter that is compatible with standard, silicon-based ultra-large-scale integration (ULSI) technology. Bulk silicon has an indirect energy bandgap and is therefore highly inefficient as a light source, necessitating the use of other materials for the optical emitters. However, the introduction of these materials is usually incompatible with the strict processing requirements of existing ULSI technologies. Moreover, as the length scale of the devices decreases, electrons will spend increasingly more of their time in the connections between components; this interconnectivity problem could restrict further increases in computer chip processing power and speed in as little as five years. Many efforts have therefore been directed, with varying degrees of success, to engineering silicon-based materials that are efficient light emitters. Here, we describe the fabrication, using standard silicon processing techniques, of a silicon light-emitting diode (LED) that operates efficiently at room temperature. Boron is implanted into silicon both as a dopant to form a p-n junction, as well as a means of introducing dislocation loops. The dislocation loops introduce a local strain field, which modifies the band structure and provides spatial confinement of the charge carriers. It is this spatial confinement which allows room-temperature electroluminescence at the band-edge. This device strategy is highly compatible with ULSI technology, as boron ion implantation is already used as a standard method for the fabrication of silicon devices.     

Mouse sex vesicle. C-band and pairing at the light and electron microscope

Summary C banded mouse pachytene chromosomes were studied with the light and electron microscopes by the whole mount technique. The X and Y chromosomes show pairing by the long, by the short or by both long and short arms. Assuming Lyon's hypothesis, the latter suggests that the Y segment transferred to the X is intercalar. With the light microscope, a negative image of the synaptonemal complex is evidenced.This work was supported by grants of the Brazilian Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Fundo Especial de Despesas do Instituto Butantan (FEDIB).We acknowledge Dr. N. Leon for his editorial suggestions.     

The DNA sequence and analysis of human chromosome 14

Chromosome 14 is one of five acrocentric chromosomes in the human genome. These chromosomes are characterized by a heterochromatic short arm that contains essentially ribosomal RNA genes, and a euchromatic long arm in which most, if not all, of the protein-coding genes are located. The finished sequence of human chromosome 14 comprises 87,410,661 base pairs, representing 100% of its euchromatic portion, in a single continuous segment covering the entire long arm with no gaps. Two loci of crucial importance for the immune system, as well as more than 60 disease genes, have been localized so far on chromosome 14. We identified 1,050 genes and gene fragments, and 393 pseudogenes. On the basis of comparisons with other vertebrate genomes, we estimate that more than 96% of the chromosome 14 genes have been annotated. From an analysis of the CpG island occurrences, we estimate that 70% of these annotated genes are complete at their 5' end.     

RGM is a repulsive guidance molecule for retinal axons

Axons rely on guidance cues to reach remote targets during nervous system development. A well-studied model system for axon guidance is the retinotectal projection. The retina can be divided into halves; the nasal half, next to the nose, and the temporal half. A subset of retinal axons, those from the temporal half, is guided by repulsive cues expressed in a graded fashion in the optic tectum, part of the midbrain. Here we report the cloning and functional characterization of a membrane-associated glycoprotein, which we call RGM (repulsive guidance molecule). This molecule shares no sequence homology with known guidance cues, and its messenger RNA is distributed in a gradient with increasing concentration from the anterior to posterior pole of the embryonic tectum. Recombinant RGM at low nanomolar concentration induces collapse of temporal but not of nasal growth cones and guides temporal retinal axons in vitro, demonstrating its repulsive and axon-specific guiding activity.     

When the American sea sturgeon swam east

The two species of Atlantic sea sturgeon on either shore of the North Atlantic, Acipenser sturio in Europe and A. oxyrinchus in North America, probably diverged with the closure of the Tethys Sea and the onset of the North Atlantic Gyre 15-20 million years ago, and contact between them was then presumably precluded by geographic distance. Here we present genetic, morphological and archaeological evidence indicating that the North American sturgeon colonized the Baltic during the Middle Ages and replaced the native sturgeon there, before recently becoming extinct itself in Europe as a result of human activities. In addition to representing a unique transatlantic colonization event by a fish that swims upriver to spawn, our findings have important implications for projects aimed at restocking Baltic waters with the European sturgeon.     

Mutant P450 oxidoreductase causes disordered steroidogenesis with and without Antley-Bixler syndrome

Deficient activities of multiple steroidogenic enzymes have been reported without and with Antley-Bixler syndrome (ABS), but mutations of corresponding cytochrome P450 enzymes have not been found. We identified mutations in POR, encoding P450 oxidoreductase, the obligate electron donor for these enzymes, in a woman with amenorrhea and three children with ABS, even though knock-out of POR is embryonically lethal in mice. Mutations of POR also affect drug-metabolizing P450 enzymes, explaining the association of ABS with maternal fluconazole ingestion.     

Morning and evening peaks of activity rely on different clock neurons of the Drosophila brain

In Drosophila, a 'clock' situated in the brain controls circadian rhythms of locomotor activity. This clock relies on several groups of neurons that express the Period (PER) protein, including the ventral lateral neurons (LN(v)s), which express the Pigment-dispersing factor (PDF) neuropeptide, and the PDF-negative dorsal lateral neurons (LN(d)s). In normal cycles of day and night, adult flies exhibit morning and evening peaks of activity; however, the contribution of the different clock neurons to the rest-activity pattern remains unknown. Here, we have used targeted expression of PER to restore the clock function of specific subsets of lateral neurons in arrhythmic per(0) mutant flies. We show that PER expression restricted to the LN(v)s only restores the morning activity, whereas expression of PER in both the LN(v)s and LN(d)s also restores the evening activity. This provides the first neuronal bases for 'morning' and 'evening' oscillators in the Drosophila brain. Furthermore, we show that the LN(v)s alone can generate 24 h activity rhythms in constant darkness, indicating that the morning oscillator is sufficient to drive the circadian system.     

The genome sequence of the plant pathogen Xylella fastidiosa. The Xylella fastidiosa Consortium of the Organization for Nucleotide Sequencing and Analysis

Xylella fastidiosa is a fastidious, xylem-limited bacterium that causes a range of economically important plant diseases. Here we report the complete genome sequence of X. fastidiosa clone 9a5c, which causes citrus variegated chlorosis--a serious disease of orange trees. The genome comprises a 52.7% GC-rich 2,679,305-base-pair (bp) circular chromosome and two plasmids of 51,158 bp and 1,285 bp. We can assign putative functions to 47% of the 2,904 predicted coding regions. Efficient metabolic functions are predicted, with sugars as the principal energy and carbon source, supporting existence in the nutrient-poor xylem sap. The mechanisms associated with pathogenicity and virulence involve toxins, antibiotics and ion sequestration systems, as well as bacterium-bacterium and bacterium-host interactions mediated by a range of proteins. Orthologues of some of these proteins have only been identified in animal and human pathogens; their presence in X. fastidiosa indicates that the molecular basis for bacterial pathogenicity is both conserved and independent of host. At least 83 genes are bacteriophage-derived and include virulence-associated genes from other bacteria, providing direct evidence of phage-mediated horizontal gene transfer.     

Defective planar cell polarity in polycystic kidney disease

Morphogenesis involves coordinated proliferation, differentiation and spatial distribution of cells. We show that lengthening of renal tubules is associated with mitotic orientation of cells along the tubule axis, demonstrating intrinsic planar cell polarization, and we demonstrate that mitotic orientations are significantly distorted in rodent polycystic kidney models. These results suggest that oriented cell division dictates the maintenance of constant tubule diameter during tubular lengthening and that defects in this process trigger renal tubular enlargement and cyst formation.