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See detailStructural basis of protein phosphatase 1 regulation
Terrak, Mohammed ULg; Kerff, Frédéric ULg; Langsetmo, K. et al

in Nature (2004), 429(6993), 780-4

The coordinated and reciprocal action of serine/threonine (Ser/Thr) protein kinases and phosphatases produces transient phosphorylation, a fundamental regulatory mechanism for many biological processes ... [more ▼]

The coordinated and reciprocal action of serine/threonine (Ser/Thr) protein kinases and phosphatases produces transient phosphorylation, a fundamental regulatory mechanism for many biological processes. The human genome encodes a far greater number of Ser/Thr protein kinases than of phosphatases. Protein phosphatase 1 (PP1), in particular, is ubiquitously distributed and regulates a broad range of cellular functions, including glycogen metabolism, cell-cycle progression and muscle relaxation. PP1 has evolved effective catalytic machinery but lacks substrate specificity. Substrate specificity is conferred upon PP1 through interactions with a large number of regulatory subunits. The regulatory subunits are generally unrelated, but most possess the RVxF motif, a canonical PP1-binding sequence. Here we reveal the crystal structure at 2.7 A resolution of the complex between PP1 and a 34-kDa N-terminal domain of the myosin phosphatase targeting subunit MYPT1. MYPT1 is the protein that regulates PP1 function in smooth muscle relaxation. Structural elements amino- and carboxy-terminal to the RVxF motif of MYPT1 are positioned in a way that leads to a pronounced reshaping of the catalytic cleft of PP1, contributing to the increased myosin specificity of this complex. The structure has general implications for the control of PP1 activity by other regulatory subunits. [less ▲]

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See detailInsight and the sleep committee
Maquet, Pierre ULg; Ruby, Perrine

in Nature (2004), 427(6972), 304-305

We all spend about a third of our lives asleep, an essential but seemingly unproductive state. Experimental evidence now emerges to support anecdotal evidence that sleep can stimulate creative thinking.

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See detailCorrigenda: The lipid phosphatase SHIP2 controls insulin sensitivity
Clément, S.; Krause, U.; Desmedt, F. et al

in Nature (2004), 431

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See detailEvolution of the polarization of the optical afterglow of the γ-ray burst GRB030329
Greiner, Jochen; Klose, Sylvio; Reinsch, Klaus et al

in Nature (2003), 426

The association of a supernova with GRB030329 strongly supports the `collapsar' model of γ-ray bursts, where a relativistic jet forms after the progenitor star collapses. Such jets cannot be spatially ... [more ▼]

The association of a supernova with GRB030329 strongly supports the `collapsar' model of γ-ray bursts, where a relativistic jet forms after the progenitor star collapses. Such jets cannot be spatially resolved because γ-ray bursts lie at cosmological distances; their existence is instead inferred from `breaks' in the light curves of the afterglows, and from the theoretical desire to reduce the estimated total energy of the burst by proposing that most of it comes out in narrow beams. Temporal evolution of the polarization of the afterglows may provide independent evidence for the jet structure of the relativistic outflow. Small-level polarization (~1-3 per cent) has been reported for a few bursts, but its temporal evolution has yet to be established. Here we report polarimetric observations of the afterglow of GRB030329. We establish the polarization light curve, detect sustained polarization at the per cent level, and find significant variability. The data imply that the afterglow magnetic field has a small coherence length and is mostly random, probably generated by turbulence, in contrast with the picture arising from the high polarization detected in the prompt γ-rays from GRB021206 (ref. 18). [less ▲]

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See detailA regulatory mutation in IGF2 causes a major QTL effect on muscle growth in the pig
Van Laere, Anne-Sophie ULg; Nguyen, Minh Ngoc ULg; Braunschweig, M. et al

in Nature (2003), 425(6960), 832-836

Most traits and disorders have a multifactorial background indicating that they are controlled by environmental factors as well as an unknown number of quantitative trait loci (QTLs)(1,2). The ... [more ▼]

Most traits and disorders have a multifactorial background indicating that they are controlled by environmental factors as well as an unknown number of quantitative trait loci (QTLs)(1,2). The identification of mutations underlying QTLs is a challenge because each locus explains only a fraction of the phenotypic variation(3,4). A paternally expressed QTL affecting muscle growth, fat deposition and size of the heart in pigs maps to the IGF2 (insulin-like growth factor 2) region(5,6). Here we show that this QTL is caused by a nucleotide substitution in intron 3 of IGF2. The mutation occurs in an evolutionarily conserved CpG island that is hypomethylated in skeletal muscle. The mutation abrogates in vitro interaction with a nuclear factor, probably a repressor, and pigs inheriting the mutation from their sire have a threefold increase in IGF2 messenger RNA expression in postnatal muscle. Our study establishes a causal relationship between a single-base-pair substitution in a non-coding region and a QTL effect. The result supports the long-held view that regulatory mutations are important for controlling phenotypic variation(7). [less ▲]

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See detailLubrication by charged polymers
Raviv, Uri; Giasson, Suzanne; Kampf, Nir et al

in Nature (2003), 425(6954), 163-165

Long-ranged forces between surfaces in a liquid control effects from colloid stability [1] to biolubrication [2], and can be modified either by steric factors due to flexible polymers [3], or by surface ... [more ▼]

Long-ranged forces between surfaces in a liquid control effects from colloid stability [1] to biolubrication [2], and can be modified either by steric factors due to flexible polymers [3], or by surface charge effects [4]. In particular, neutral polymer 'brushes' may lead to a massive reduction in sliding friction between the surfaces to which they are attached [5-7], whereas hydrated ions can act as extremely efficient lubricants between sliding charged surfaces [8]. Here we show that brushes of charged polymers (polyelectrolytes) attached to surfaces rubbing across an aqueous medium result in superior lubrication compared to other polymeric surfactants. Effective friction coefficients with polyelectrolyte brushes in water are lower than about 0.0006-0.001 even at low sliding velocities and at pressures of up to several atmospheres (typical of those in living systems). We attribute this to the exceptional resistance to mutual interpenetration displayed by the compressed, counterion-swollen brushes, together with the fluidity of the hydration layers surrounding the charged, rubbing polymer segments. Our findings may have implications for biolubrication effects, which are important in the design of lubricated surfaces in artificial implants, and in understanding frictional processes in biological systems. [less ▲]

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See detailA camelid antibody fragment inhibits the formation of amyloid fibrils by human lysozyme
Dumoulin, Mireille ULg; Last, A. M.; Desmyter, A. et al

in Nature (2003), 424(6950), 783-788

Amyloid diseases are characterized by an aberrant assembly of a specific protein or protein fragment into fibrils and plaques that are deposited in various organs and tissues(1-3), often with serious ... [more ▼]

Amyloid diseases are characterized by an aberrant assembly of a specific protein or protein fragment into fibrils and plaques that are deposited in various organs and tissues(1-3), often with serious pathological consequences. Non-neuropathic systemic amyloidosis (4-6) is associated with single point mutations in the gene coding for human lysozyme. Here we report that a single-domain fragment of a camelid antibody(7-9) raised against wild-type human lysozyme inhibits the in vitro aggregation of its amyloidogenic variant, D67H. Our structural studies reveal that the epitope includes neither the site of mutation nor most residues in the region of the protein structure that is destabilized by the mutation. Instead, the binding of the antibody fragment achieves its effect by restoring the structural cooperativity characteristic of the wild-type protein. This appears to occur at least in part through the transmission of long-range conformational effects to the interface between the two structural domains of the protein. Thus, reducing the ability of an amyloidogenic protein to form partly unfolded species can be an effective method of preventing its aggregation, suggesting approaches to the rational design of therapeutic agents directed against protein deposition diseases. [less ▲]

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See detailCritical thickness for ferroelectricity in perovskite ultrathin films
Junquera, J.; Ghosez, Philippe ULg

in Nature (2003), 422(6931), 506-509

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See detailApolipoprotein L-I is the trypanosome lytic factor of human serum.
Vanhamme, Luc; Paturiaux-Hanocq, Francoise; Poelvoorde, Philippe et al

in Nature (2003), 422(6927), 83-7

Human sleeping sickness in east Africa is caused by the parasite Trypanosoma brucei rhodesiense. The basis of this pathology is the resistance of these parasites to lysis by normal human serum (NHS ... [more ▼]

Human sleeping sickness in east Africa is caused by the parasite Trypanosoma brucei rhodesiense. The basis of this pathology is the resistance of these parasites to lysis by normal human serum (NHS). Resistance to NHS is conferred by a gene that encodes a truncated form of the variant surface glycoprotein termed serum resistance associated protein (SRA). We show that SRA is a lysosomal protein, and that the amino-terminal alpha-helix of SRA is responsible for resistance to NHS. This domain interacts strongly with a carboxy-terminal alpha-helix of the human-specific serum protein apolipoprotein L-I (apoL-I). Depleting NHS of apoL-I, by incubation with SRA or anti-apoL-I, led to the complete loss of trypanolytic activity. Addition of native or recombinant apoL-I either to apoL-I-depleted NHS or to fetal calf serum induced lysis of NHS-sensitive, but not NHS-resistant, trypanosomes. Confocal microscopy demonstrated that apoL-I is taken up through the endocytic pathway into the lysosome. We propose that apoL-I is the trypanosome lytic factor of NHS, and that SRA confers resistance to lysis by interaction with apoL-I in the lysosome. [less ▲]

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See detailUltraviolet emissions from the magnetic footprints of Io, Ganymede and Europa on Jupiter
Clarke, J. T.; Ajello, Joseph M.; Ballester, G. et al

in Nature (2002), 415(6875), 997-1000

Io leaves a magnetic footprint on Jupiter's upper atmosphere that appears as a spot of ultraviolet emission that remains fixed underneath Io as Jupiter rotates(1-3). The specific physical mechanisms ... [more ▼]

Io leaves a magnetic footprint on Jupiter's upper atmosphere that appears as a spot of ultraviolet emission that remains fixed underneath Io as Jupiter rotates(1-3). The specific physical mechanisms responsible for generating those emissions are not well understood, but in general the spot seems to arise because of an electromagnetic interaction between Jupiter's magnetic field and the plasma surrounding Io, driving currents of around 1 million amperes down through Jupiter's ionosphere(4-6). The other galilean satellites may also leave footprints, and the presence or absence of such footprints should illuminate the underlying physical mechanism by revealing the strengths of the currents linking the satellites to Jupiter. Here we report persistent, faint, far-ultraviolet emission from the jovian footprints of Ganymede and Europa. We also show that Io's magnetic footprint extends well beyond the immediate vicinity of Io's flux-tube interaction with Jupiter, and much farther than predicted theoretically(4-6); the emission persists for several hours downstream. We infer from these data that Ganymede and Europa have persistent interactions with Jupiter's magnetic field despite their thin atmospheres. [less ▲]

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See detailTransient aurora on Jupiter from injections of magnetospheric electrons
Mauk, B. H.; Clarke, J. T.; Grodent, Denis ULg et al

in Nature (2002), 415(6875), 1003-1005

Energetic electrons and ions that are trapped in Earth's magnetosphere can suddenly be accelerated towards the planet(1-5). Some dynamic features of Earth's aurora (the northern and southern lights) are ... [more ▼]

Energetic electrons and ions that are trapped in Earth's magnetosphere can suddenly be accelerated towards the planet(1-5). Some dynamic features of Earth's aurora (the northern and southern lights) are created by the fraction of these injected particles that travels along magnetic field lines and hits the upper atmosphere(4). Jupiter's aurora appears similar to Earth's in some respects; both appear as large ovals circling the poles and both show transient events(6-11). But the magnetospheres of Jupiter and Earth are so different-particularly in the way they are powered-that it is not known whether the magnetospheric drivers(12) of Earth's aurora also cause them on Jupiter. Here we show a direct relationship between Earth-like injections of electrons in Jupiter's magnetosphere and a transient auroral feature in Jupiter's polar region. This relationship is remarkably similar to what happens at Earth, and therefore suggests that despite the large differences between planetary magnetospheres, some processes that generate aurorae are the same throughout the Solar System. [less ▲]

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See detailA pulsating auroral X-ray hot spot on Jupiter
Gladstone, G. R.; Waite, J. H.; Grodent, Denis ULg et al

in Nature (2002), 415(6875), 1000-1003

Jupiter's X-ray aurora has been thought to be excited by energetic sulphur and oxygen ions precipitating from the inner magnetosphere into the planet's polar regions(1-3). Here we report high-spatial ... [more ▼]

Jupiter's X-ray aurora has been thought to be excited by energetic sulphur and oxygen ions precipitating from the inner magnetosphere into the planet's polar regions(1-3). Here we report high-spatial-resolution observations that demonstrate that most of Jupiter's northern auroral X-rays come from a 'hot spot' located significantly poleward of the latitudes connected to the inner magnetosphere. The hot spot seems to be fixed in magnetic latitude and longitude and occurs in a region where anomalous infrared(4-7) and ultraviolet(8) emissions have also been observed. We infer from the data that the particles that excite the aurora originate in the outer magnetosphere. The hot spot X-rays pulsate with an approximately 45-min period, a period similar to that reported for high-latitude radio and energetic electron bursts observed by near-Jupiter spacecraft(9,10). These results invalidate the idea that jovian auroral X-ray emissions are mainly excited by steady precipitation of energetic heavy ions from the inner magnetosphere. Instead, the X-rays seem to result from currently unexplained processes in the outer magnetosphere that produce highly localized and highly variable emissions over an extremely wide range of wavelengths. [less ▲]

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See detailMorphological and ecological complexity in early eukaryotic ecosystems
Javaux, Emmanuelle ULg; Knoll, A. H.; Walter, M. R.

in Nature (2001), 412(6842), 66-69

Molecular phylogeny and biogeochemistry indicate that eukaryotes differentiated early in Earth history. Sequence comparisons of small-subunit ribosomal RNA genes suggest a deep evolutionary divergence of ... [more ▼]

Molecular phylogeny and biogeochemistry indicate that eukaryotes differentiated early in Earth history. Sequence comparisons of small-subunit ribosomal RNA genes suggest a deep evolutionary divergence of Eukarya and Archaea(1); C-27-C-29 steranes (derived from sterols synthesized by eukaryotes) and strong depletion of C-13 (a biogeochemical signature of methanogenic Archaea) in 2,700 Myr old kerogens independently place a minimum age on this split(2,3). Steranes, large spheroidal microfossils, and rare macrofossils of possible eukaryotic origin occur in Palaeoproterozoic rocks(4-6). Until now, however, evidence for morphological and taxonomic diversification within the domain has generally been restricted to very late Mesoproterozoic and Neoproterozoic successions(7). Here we show that the cytoskeletal and ecological prerequisites for eukaryotic diversification were already established in eukaryotic microorganisms fossilized nearly 1,500 Myr ago in shales of the early Mesoproterozoic Roper Group in northern Australia. [less ▲]

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See detailThe lipid phosphatase SHIP2 controls insulin sensitivity
Clément, S.; Krause, U.; Desmedt, F. et al

in Nature (2001), 409

Insulin is the primary hormone involved in glucose homeostasis, and impairment of insulin action and/or secretion has a critical role in the pathogenesis of diabetes mellitus. Type-II SH2-domain ... [more ▼]

Insulin is the primary hormone involved in glucose homeostasis, and impairment of insulin action and/or secretion has a critical role in the pathogenesis of diabetes mellitus. Type-II SH2-domain-containing inositol 5-phosphatase, or 'SHIP2', is a member of the inositol polyphosphate 5-phosphatase family. In vitro studies have shown that SHIP2, in response to stimulation by numerous growth factors and insulin, is closely linked to signalling events mediated by both phosphoinositide-3-OH kinase and Ras/mitogen-activated protein kinase. Here we report the generation of mice lacking the SHIP2 gene. Loss of SHIP2 leads to increased sensitivity to insulin, which is characterized by severe neonatal hypoglycaemia, deregulated expression of the genes involved in gluconeogenesis, and perinatal death. Adult mice that are heterozygous for the SHIP2 mutation have increased glucose tolerance and insulin sensitivity associated with an increased recruitment of the GLUT4 glucose transporter and increased glycogen synthesis in skeletal muscles. Our results show that SHIP2 is a potent negative regulator of insulin signalling and insulin sensitivity in vivo [less ▲]

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See detailRespiration As The Main Determinant Of Carbon Balance In European Forests
Valentini, R.; Matteucci, G.; Dolman, Aj. et al

in Nature (2000), 404(6780),

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See detailEvidence for decoupling of atmospheric CO2 and global climate during the Phanerozoic eon
Veizer, J.; Godderis, Y.; François, Louis ULg

in Nature (2000), 408(6813), 698-701

Atmospheric carbon dioxide concentrations are believed to drive climate changes from glacial to interglacial modes', although geological(1-3) and astronomical(4-6) mechanisms have been invoked as ultimate ... [more ▼]

Atmospheric carbon dioxide concentrations are believed to drive climate changes from glacial to interglacial modes', although geological(1-3) and astronomical(4-6) mechanisms have been invoked as ultimate causes. Additionally, it is unclear(7,8) whether the changes between cold and warm modes should be regarded as a global phenomenon, affecting tropical and high-latitude temperatures alike(9-13), or if they are better described as an expansion and contraction of the latitudinal climate zones, keeping equatorial temperatures approximately constant(14-16). Here we present a reconstruction of tropical sea surface temperatures throughout the phanerozoic eon (the past similar to 550 Myr) from our database(17) of oxygen isotopes in calcite and aragonite shells. The data indicate large oscillations of tropical sea surface temperatures in phase with the cold-warm cycles, thus favouring the idea of climate variability as a global phenomenon. But our data conflict with a temperature reconstruction using an energy balance model that is forced by reconstructed atmospheric carbon dioxide concentrations(18). The results can be reconciled if atmospheric carbon dioxide concentrations were not the principal driver of climate variability on geological timescales for at least one-third of the Phanerozoic eon, or if the reconstructed carbon dioxide concentrations are not reliable. [less ▲]

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See detailSeismic hazard in the Sea of Marmara following the Izmit Earthquake
Hubert, Aurelia ULg; Barka, Aykut; Jacques, Eric et al

in Nature (2000), 404

On 17 August 1999, a destructive magnitude 7.4 earthquake occurred 100 km east of Istanbul, near the city of Izmit, on the North Anatolian fault. This 1,600-km-long plate boundary1,2 slips at an average ... [more ▼]

On 17 August 1999, a destructive magnitude 7.4 earthquake occurred 100 km east of Istanbul, near the city of Izmit, on the North Anatolian fault. This 1,600-km-long plate boundary1,2 slips at an average rate of 2–3 cm yr−1 (refs 3–5), and historically has been the site of many devastating earthquakes6,7. This century alone it has ruptured over 900 km of its length6. Models of earthquake-induced stress change8 combined with active fault maps9 had been used to forecast that the epicentral area of the 1999 Izmit event was indeed a likely location for the occurrence of a large earthquake9,10. Here we show that the 1999 event itself significantly modifies the stress distribution resulting from pre- vious fault interactions9,10. Our new stress models take into account all events in the region with magnitudes greater than 6 having occurred since 1700 (ref. 7) as well as secular interseismic stress change, constrained by GPS data11. These models provide a consistent picture of the long term spatio–temporal behaviour of the North Anatolian fault and indicate that two events of magnitude equal to, or greater than, the Izmit earthquake are likely to occur within the next decades beneath the Marmara Sea, south of Istanbul. [less ▲]

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See detailSequence and analysis of chromosome 4 of the plant Arabidopsis thaliana.
Mayer, K.; Portetelle, Daniel ULg; Vandenbol, Micheline ULg et al

in Nature (1999), 402

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See detailThe Nucleotide Sequence Of Saccharomyces Cerevisiae Chromosome Xv
Dujon, B.; Albermann, K.; Aldea, M. et al

in Nature (1997), 387(6632),

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See detailThe Complete Genome Sequence Of The Gram-Positive Bacterium Bacillus Subtilis
Kunst, F.; Ogasawara, N.; Moszer, I. et al

in Nature (1997), 390(6657), 249-256

Bacillus subtilis is the best-characterized member of the Gram-positive bacteria. Its genome of 4,214,810 base pairs comprises 4,100 protein-coding genes. Of these protein-coding genes, 53% are ... [more ▼]

Bacillus subtilis is the best-characterized member of the Gram-positive bacteria. Its genome of 4,214,810 base pairs comprises 4,100 protein-coding genes. Of these protein-coding genes, 53% are represented once, while a quarter of the genome corresponds to several gene families that have been greatly expanded by gene duplication, the largest family containing 77 putative ATP-binding transport proteins. In addition, a large proportion of the genetic capacity is devoted to the utilization of a variety of carbon sources, including many plant-derived molecules. The identification of five signal peptidase genes, as well as several genes for components of the secretion apparatus, is important given the capacity of Bacillus strains to secrete large amounts of industrially important enzymes. Many of the genes are involved in the synthesis of secondary metabolites, including antibiotics, that are more typically associated with Streptomyces species. The genome contains at least ten prophages or remnants of prophages, indicating that bacteriophage infection has played an important evolutionary role in horizontal gene transfer, in particular in the propagation of bacterial pathogenesis. [less ▲]

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