XIAP deficiency in humans causes an X-linked lymphoproliferative syndrome

The homeostasis of the immune response requires tight regulation of the proliferation and apoptosis of activated lymphocytes. In humans, defects in immune homeostasis result in lymphoproliferation disorders including autoimmunity, haemophagocytic lymphohystiocytosis and lymphomas. The X-linked lymphoproliferative syndrome (XLP) is a rare, inherited immunodeficiency that is characterized by lymphohystiocytosis, hypogammaglobulinaemia and lymphomas, and that usually develops in response to infection with Epstein-Barr virus (EBV). Mutations in the signalling lymphocyte activation molecule (SLAM)-associated protein SAP, a signalling adaptor molecule, underlie 60% of cases of familial XLP. Here, we identify mutations in the gene that encodes the X-linked inhibitor-of-apoptosis XIAP (also termed BIRC4) in patients with XLP from three families without mutations in SAP. These mutations lead to defective expression of XIAP. We show that apoptosis of lymphocytes from XIAP-deficient patients is enhanced in response to various stimuli including the T-cell antigen receptor (TCR)-CD3 complex, the death receptor CD95 (also termed Fas or Apo-1) and the TNF-associated apoptosis-inducing ligand receptor (TRAIL-R). We also found that XIAP-deficient patients, like SAP-deficient patients, have low numbers of natural killer T-lymphocytes (NKT cells), indicating that XIAP is required for the survival and/or differentiation of NKT cells. The observation that XIAP-deficiency and SAP-deficiency are both associated with a defect in NKT cells strengthens the hypothesis that NKT cells have a key role in the immune response to EBV. Furthermore, by identifying an XLP immunodeficiency that is caused by mutations in XIAP, we show that XIAP is a potent regulator of lymphocyte homeostasis in vivo.     

Record of mid-Archaean subduction from metamorphism in the Barberton terrain, South Africa

Although plate tectonics is the central geological process of the modern Earth, its form and existence during the Archaean era (4.0-2.5 Gyr ago) are disputed. The existence of subduction during this time is particularly controversial because characteristic subduction-related mineral assemblages, typically documenting apparent geothermal gradients of 15 degrees C km(-1) or less, have not yet been recorded from in situ Archaean rocks (the lowest recorded apparent geothermal gradients are greater than 25 degrees C km(-1)). Despite this absence from the rock record, low Archaean geothermal gradients are suggested by eclogitic nodules in kimberlites and circumstantial evidence for subduction processes, including possible accretion-related structures, has been reported in Archaean terrains. The lack of spatially and temporally well-constrained high-pressure, low-temperature metamorphism continues, however, to cast doubt on the relevance of subduction-driven tectonics during the first 1.5 Gyr of the Earth's history. Here we report garnet-albite-bearing mineral assemblages that record pressures of 1.2-1.5 GPa at temperatures of 600-650 degrees C from supracrustal amphibolites from the mid-Archaean Barberton granitoid-greenstone terrain. These conditions point to apparent geothermal gradients of 12-15 degrees C-similar to those found in recent subduction zones-that coincided with the main phase of terrane accretion in the structurally overlying Barberton greenstone belt. These high-pressure, low-temperature conditions represent metamorphic evidence for cold and strong lithosphere, as well as subduction-driven tectonic processes, during the evolution of the early Earth.     

No signature of clear CO2 ice from the 'cryptic' regions in Mars' south seasonal polar cap

The seasonal polar ice caps of Mars are composed mainly of CO2 ice. A region of low (< 30%) albedo has been observed within the south seasonal cap during early to mid-spring. The low temperature of this 'cryptic region' has been attributed to a clear slab of nearly pure CO2 ice, with the low albedo resulting from absorption by the underlying surface. Here we report near-infrared imaging spectroscopy of the south seasonal cap. The deep and broad CO2 absorption bands that are expected in the near-infrared with a thick transparent slab of CO2 ice are not observed. Models of the observed spectra indicate that the low albedo results from extensive dust contamination close to the surface of a CO2 ice layer, which could be linked to atmospheric circulation patterns. The strength of the CO2 absorption increases after mid-spring, so part of the dust is either carried away or buried more deeply in the ice layer during the CO2 ice sublimation process.     

Continental-scale patterns of canopy tree composition and function across Amazonia

The world's greatest terrestrial stores of biodiversity and carbon are found in the forests of northern South America, where large-scale biogeographic patterns and processes have recently begun to be described. Seven of the nine countries with territory in the Amazon basin and the Guiana shield have carried out large-scale forest inventories, but such massive data sets have been little exploited by tropical plant ecologists. Although forest inventories often lack the species-level identifications favoured by tropical plant ecologists, their consistency of measurement and vast spatial coverage make them ideally suited for numerical analyses at large scales, and a valuable resource to describe the still poorly understood spatial variation of biomass, diversity, community composition and forest functioning across the South American tropics. Here we show, by using the seven forest inventories complemented with trait and inventory data collected elsewhere, two dominant gradients in tree composition and function across the Amazon, one paralleling a major gradient in soil fertility and the other paralleling a gradient in dry season length. The data set also indicates that the dominance of Fabaceae in the Guiana shield is not necessarily the result of root adaptations to poor soils (nodulation or ectomycorrhizal associations) but perhaps also the result of their remarkably high seed mass there as a potential adaptation to low rates of disturbance.     

Transport synaptosomal du Tryptophane et de la Tyrosine cérébrale. Existence de systèmes de capture d'affinité différente

Summary The existence of low and high affinity systems for tryptophan and tyrosine uptake by synaptosomes were demonstrated in vitro in the rat mesencephalon.

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Ce travail réalisé dans le laboratoire du ProfesseurM. Jouvet a bénéficié de l'aide de l'I.N.S.E.R.M. (No. U-52), de la D.R.M.E. (contrat No. 72-108) et du C.N.R.S. (Laboratoire associé No. 162).

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Nous remercions tout particulièrement MmeG. Veuillet et MmeR. Juruguen pour leur précieuse aide technique.     

Disruption of CREB function in brain leads to neurodegeneration

Control of cellular survival and proliferation is dependent on extracellular signals and is a prerequisite for ordered tissue development and maintenance. Activation of the cAMP responsive element binding protein (CREB) by phosphorylation has been implicated in the survival of mammalian cells. To define its roles in the mouse central nervous system, we disrupted Creb1 in brain of developing and adult mice using the Cre/loxP system. Mice with a Crem(-/-) background and lacking Creb in the central nervous system during development show extensive apoptosis of postmitotic neurons. By contrast, mice in which both Creb1 and Crem are disrupted in the postnatal forebrain show progressive neurodegeneration in the hippocampus and in the dorsolateral striatum. The striatal phenotype is reminiscent of Huntington disease and is consistent with the postulated role of CREB-mediated signaling in polyglutamine-triggered diseases.     

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.