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Showing papers by "Centre national de la recherche scientifique published in 1998"


Journal ArticleDOI
TL;DR: The Crystallography & NMR System (CNS) as mentioned in this paper is a software suite for macromolecular structure determination by X-ray crystallography or solution nuclear magnetic resonance (NMR) spectroscopy.
Abstract: A new software suite, called Crystallography & NMR System (CNS), has been developed for macromolecular structure determination by X-ray crystallography or solution nuclear magnetic resonance (NMR) spectroscopy. In contrast to existing structure-determination programs the architecture of CNS is highly flexible, allowing for extension to other structure-determination methods, such as electron microscopy and solid-state NMR spectroscopy. CNS has a hierarchical structure: a high-level hypertext markup language (HTML) user interface, task-oriented user input files, module files, a symbolic structure-determination language (CNS language), and low-level source code. Each layer is accessible to the user. The novice user may just use the HTML interface, while the more advanced user may use any of the other layers. The source code will be distributed, thus source-code modification is possible. The CNS language is sufficiently powerful and flexible that many new algorithms can be easily implemented in the CNS language without changes to the source code. The CNS language allows the user to perform operations on data structures, such as structure factors, electron-density maps, and atomic properties. The power of the CNS language has been demonstrated by the implementation of a comprehensive set of crystallographic procedures for phasing, density modification and refinement. User-friendly task-oriented input files are available for nearly all aspects of macromolecular structure determination by X-ray crystallography and solution NMR.

15,182 citations


Journal ArticleDOI
TL;DR: The acquisition of the biochemical and ultrastructural features of apoptosis critically relies on the liberation of apoptogenic proteases or protease activators from mitochondria.
Abstract: Both physiological cell death (apoptosis) and, in some cases, accidental cell death (necrosis) involve a two-step process. At a first level, numerous physiological and some pathological stimuli trigger an increase in mitochondrial membrane permeability. The mitochondria release apoptogenic factors through the outer membrane and dissipate the electrochemical gradient of the inner membrane. Mitochondrial permeability transition (PT) involves a dynamic multiprotein complex formed in the contact site between the inner and outer mitochondrial membranes. The PT complex can function as a sensor for stress and damage, as well as for certain signals connected to receptors. Inhibition of PT by pharmacological intervention on mitochondrial structures or mitochondrial expression of the apoptosis-inhibitory oncoprotein Bcl-2 prevents cell death, suggesting that PT is a rate-limiting event of the death process. At a second level, the consequences of mitochondrial dysfunction (collapse of the mitochondrial inner transmembrane potential, uncoupling of the respiratory chain, hyperproduction of superoxide anions, disruption of mitochondrial biogenesis, outflow of matrix calcium and glutathione, and release of soluble intermembrane proteins) entails a bioenergetic catastrophe culminating in the disruption of plasma membrane integrity (necrosis) and/or the activation of specific apoptogenic proteases (caspases) by mitochondrial proteins that leak into the cytosol (cytochrome c, apoptosis-inducing factor) with secondary endonuclease activation (apoptosis). The relative rate of these two processes (bioenergetic catastrophe versus protease and endonuclease activation) determines whether a cell will undergo primary necrosis or apoptosis. The acquisition of the biochemical and ultrastructural features of apoptosis critically relies on the liberation of apoptogenic proteases or protease activators from mitochondria. The fact that mitochondrial events control cell death has major implications for the development of cytoprotective and cytotoxic drugs.

2,034 citations


Journal ArticleDOI
01 Oct 1998
TL;DR: The objectives of this paper are to review some of the approaches that have been developed to address blind signal separation and independent component analysis, to illustrate how they stem from basic principles, and to show how they relate to each other.
Abstract: Blind signal separation (BSS) and independent component analysis (ICA) are emerging techniques of array processing and data analysis that aim to recover unobserved signals or "sources" from observed mixtures (typically, the output of an array of sensors), exploiting only the assumption of mutual independence between the signals. The weakness of the assumptions makes it a powerful approach, but it requires us to venture beyond familiar second order statistics, The objectives of this paper are to review some of the approaches that have been developed to address this problem, to illustrate how they stem from basic principles, and to show how they relate to each other.

1,890 citations


Journal ArticleDOI
TL;DR: This review will focus first on the present understanding of the structures of amylose and amylopectin and their organization within the granule, and then on the biosynthetic mechanisms explaining the biogenesis of starch in plants.

1,839 citations


Journal ArticleDOI
TL;DR: In this paper, a method for measuring and mapping displacement fields and strain fields from high-resolution electron microscope (HREM) images is developed based upon centring a small aperture around a strong reflection in the Fourier transform of an HREM lattice image and performing an inverse Fourier transformation.

1,828 citations


Journal ArticleDOI
TL;DR: In this article, phase diagrams of hydrous mid-ocean ridge (MOR) basalts to 330 km depth and hydrous peridotites to 250 km depth are compiled for conditions characteristic for subduction zones.

1,763 citations


Journal ArticleDOI
TL;DR: The possibility that the mechanism originally involved in the maintenance of the symbiosis between the bacterial ancestor of the mitochondria and the host cell precursor of eukaryotes provided the basis for the actual mechanism controlling cell survival is discussed.
Abstract: Programmed cell death serves as a major mechanism for the precise regulation of cell numbers and as a defense mechanism to remove unwanted and potentially dangerous cells. Despite the striking heterogeneity of cell death induction pathways, the execution of the death program is often associated with characteristic morphological and biochemical changes, and this form of programmed cell death has been termed apoptosis. Genetic studies in Caenorhabditis elegans had led to the identification of cell death genes (ced). The genes ced-3 and ced-4 are essential for cell death; ced-9 antagonizes the activities of ced-3 and ced-4, and thereby protects cells that should survive from any accidental activation of the death program. Caspases (cysteine aspartases) are the mammalian homologues of CED-3. CED-9 protein is homologous to a family of many members termed the Bcl-2 family (Bcl-2s) in reference to the first discovered mammalian cell death regulator. In both worm and mammalian cells, the antiapoptotic members of the Bcl-2 family act upstream of the execution caspases somehow preventing their proteolytic processing into active killers. Two main mechanisms of action have been proposed to connect Bcl-2s to caspases. In the first one, antiapoptotic Bcl-2s would maintain cell survival by dragging caspases to intracellular membranes (probably the mitochondrial membrane) and by preventing their activation. The recently described mammalian protein Apaf-1 (apoptosis protease-activating factor 1) could be the mammalian equivalent of CED-4 and could be the physical link between Bcl-2s and caspases. In the second one, Bcl-2 would act by regulating the release from mitochondria of some caspases activators: cytochrome c and/or AIF (apoptosis-inducing factor). This crucial position of mitochondria in programmed cell death control is reinforced by the observation that mitochondria contribute to apoptosis signaling via the production of reactive oxygen species. Although for a long time the absence of mitochondrial changes was considered as a hallmark of apoptosis, mitochondria appear today as the central executioner of programmed cell death. In this review, we examine the data concerning the mitochondrial features of apoptosis. Furthermore, we discuss the possibility that the mechanism originally involved in the maintenance of the symbiosis between the bacterial ancestor of the mitochondria and the host cell precursor of eukaryotes, provided the basis for the actual mechanism controlling cell survival.

1,520 citations


Journal ArticleDOI
TL;DR: In this genetic test, the involvement of a signaling cascade offers the unique property that association between the hybrid proteins can be spatially separated from the transcriptional activation readout, allowing a versatile design of screening procedures either for ligands that bind to a given "bait," as in the classical yeast two-hybrid system, or for molecules or mutations that block a given interaction between two proteins of interest.
Abstract: We describe a bacterial two-hybrid system that allows an easy in vivo screening and selection of functional interactions between two proteins. This genetic test is based on the reconstitution, in an Escherichia coli cya strain, of a signal transduction pathway that takes advantage of the positive control exerted by cAMP. Two putative interacting proteins are genetically fused to two complementary fragments, T25 and T18, that constitute the catalytic domain of Bordetella pertussis adenylate cyclase. Association of the two-hybrid proteins results in functional complementation between T25 and T18 fragments and leads to cAMP synthesis. Cyclic AMP then triggers transcriptional activation of catabolic operons, such as lactose or maltose, that yield a characteristic phenotype. In this genetic test, the involvement of a signaling cascade offers the unique property that association between the hybrid proteins can be spatially separated from the transcriptional activation readout. This permits a versatile design of screening procedures either for ligands that bind to a given “bait,” as in the classical yeast two-hybrid system, or for molecules or mutations that block a given interaction between two proteins of interest.

1,492 citations


Journal ArticleDOI
01 Nov 1998-Nature
TL;DR: In this article, it has been suggested that C60 may be trapped inside a nanotube during this elaborate sequence, but this has not been detected. But it has not yet been confirmed.
Abstract: Pulsed laser vaporization of graphite in the presence of certain metallic catalysts produces both carbon nanotubes and C60 molecules1. In nanotube production, most of the C60 is removed, along with other residual contaminants, by purification and annealing. It has been suggested that C60 may be trapped inside a nanotube during this elaborate sequence, but this has not been detected.

1,269 citations


Journal ArticleDOI
01 Aug 1998-Immunity
TL;DR: Findings indicate that Caspase 8 plays a necessary and nonredundant role in death induction by several receptors of the TNF/NGF family and serves a vital role in embryonal development.

1,228 citations


Journal ArticleDOI
01 Jun 1998
TL;DR: Substantial evidence points to the importance of reversible protein phosphorylation and modifications of cytosolic calcium levels and pH as intermediates in ABA signal transduction.
Abstract: The plant hormone abscisic acid (ABA) plays a major role in seed maturation and germination, as well as in adaptation to abiotic environmental stresses. ABA promotes stomatal closure by rapidly altering ion fluxes in guard cells. Other ABA actions involve modifications of gene expression, and the analysis of ABA-responsive promoters has revealed a diversity of potential cis-acting regulatory elements. The nature of the ABA receptor(s) remains unknown. In contrast, combined biophysical, genetic, and molecular approaches have led to considerable progress in the characterization of more downstream signaling elements. In particular, substantial evidence points to the importance of reversible protein phosphorylation and modifications of cytosolic calcium levels and pH as intermediates in ABA signal transduction. Exciting advances are being made in reassembling individual components into minimal ABA signaling cascades at the single-cell level.

Journal ArticleDOI
25 Sep 1998-Science
TL;DR: The proapoptotic molecule Bax and the constitutive mitochondrial protein ANT cooperate within the PTPC to increase mitochondrial membrane permeability and to trigger cell death.
Abstract: The proapoptotic Bax protein induces cell death by acting on mitochondria. Bax binds to the permeability transition pore complex (PTPC), a composite proteaceous channel that is involved in the regulation of mitochondrial membrane permeability. Immunodepletion of Bax from PTPC or purification of PTPC from Bax-deficient mice yielded a PTPC that could not permeabilize membranes in response to atractyloside, a proapoptotic ligand of the adenine nucleotide translocator (ANT). Bax and ANT coimmunoprecipitated and interacted in the yeast two-hybrid system. Ectopic expression of Bax induced cell death in wild-type but not in ANT-deficient yeast. Recombinant Bax and purified ANT, but neither of them alone, efficiently formed atractyloside-responsive channels in artificial membranes. Hence, the proapoptotic molecule Bax and the constitutive mitochondrial protein ANT cooperate within the PTPC to increase mitochondrial membrane permeability and to trigger cell death.

Journal ArticleDOI
TL;DR: Reactions based on lipase catalysis usually proceed with high regio- and enantioselectivity, and the Ca2+ antagonist diltiazem was obtained with lipase from Serratia marcescens.
Abstract: Unusually versatile substrate specificity is shown by lipases. Not only do they hydrolyze triacylglycerols-for example, in the stomach and intestine during digestion of dietary fat-and various synthetic esters and amides, but their high stability in organic solvents permits their use in transesterification reactions and ester synthesis as well. Reactions based on lipase catalysis usually proceed with high regio- and enantioselectivity. Thus, the Ca2+ antagonist diltiazem (1) was obtained with lipase from Serratia marcescens. Over 30 lipases have been cloned in the last few years. Since the tertiary structure of 12 lipases is known, there are presently significant efforts to improve this class of enzymes by protein engineering techniques, in view of their use in detergents and other fields of industrial application.

Journal ArticleDOI
TL;DR: In this article, the authors proposed that the observed resistance changes are due to excitations of zero-wave-number spin waves in the magnetic layers, induced by a high current density injected into the multilayer through a point contact.
Abstract: We describe variations in the resistance of $\mathrm{Co}/\mathrm{Cu}$ multilayers, induced by means of a high current density $\ensuremath{\approx}{10}^{8}\mathrm{A}/{\mathrm{cm}}^{2}$ injected into the multilayer through a point contact. We propose that the observed resistance changes are due to excitations of zero-wave-number spin waves in the magnetic layers. As predicted, such current-driven excitation of a magnetic multilayer occurs for only one direction of current flow and has a current threshold which increases linearly with the applied magnetic field.

Journal ArticleDOI
TL;DR: A minimal hypothesis is proposed concerning the brain processes underlying effortful tasks and predictions for spatio-temporal activation patterns during brain imaging are outlined, particularly about the contribution of dorsolateral cortex and anterior cingulate to the workspace.
Abstract: A minimal hypothesis is proposed concerning the brain processes underlying effortful tasks. It distinguishes two main computational spaces: a unique global workspace composed of distributed and heavily interconnected neurons with long-range axons, and a set of specialized and modular perceptual, motor, memory, evaluative, and attentional processors. Workspace neurons are mobilized in effortful tasks for which the specialized processors do not suffice. They selectively mobilize or suppress, through descending connections, the contribution of specific processor neurons. In the course of task performance, workspace neurons become spontaneously coactivated, forming discrete though variable spatio-temporal patterns subject to modulation by vigilance signals and to selection by reward signals. A computer simulation of the Stroop task shows workspace activation to increase during acquisition of a novel task, effortful execution, and after errors. We outline predictions for spatio-temporal activation patterns during brain imaging, particularly about the contribution of dorsolateral prefrontal cortex and anterior cingulate to the workspace.

Journal ArticleDOI
05 Feb 1998-Nature
TL;DR: It is shown here that the histone deacetylase HDAC1 physically interacts and cooperates with Rb, and that the Rb/HDAC1 complex is a key element in the control of cell proliferation and differentiation and that it is a likely target for transforming viruses.
Abstract: The retinoblastoma tumour-suppressor protein Rb inhibits cell proliferation by repressing a subset of genes that are controlled by the E2F family of transcription factors and which are involved in progression from the G1 to the S phase of the cell cycle. Rb, which is recruited to target promoters by E2F1, represses transcription by masking the E2F1 transactivation domain and by inhibiting surrounding enhancer elements, an active repression that could be crucial for the proper control of progression through the cell cycle. Some transcriptional regulators act by acetylating or deacetylating the tails protruding from the core histones, thereby modulating the local structure of chromatin: for example, some transcriptional repressors function through the recruitment of histone deacetylases. We show here that the histone deacetylase HDAC1 physically interacts and cooperates with Rb. In HDAC1, the sequence involved is an LXCXE motif, similar to that used by viral transforming proteins to contact Rb. Our results strongly suggest that the Rb/HDAC1 complex is a key element in the control of cell proliferation and differentiation and that it is a likely target for transforming viruses.

Journal ArticleDOI
TL;DR: The results provide strong evidence that PARP is a member of a BER multiprotein complex involved in the detection of DNA interruptions and possibly in the recruitment of XRCC1 and its partners for efficient processing of these breaks in a coordinated manner.
Abstract: The genomic integrity of cells is controlled by a network of protein factors that assess the status of the genome and either cause progression of proliferation or induce a halt in the cell cycle. In eukaryotes, DNA strand breaks, introduced either directly by ionizing radiation or indirectly following enzymatic incision of a DNA lesion, trigger the synthesis of poly(ADP-ribose) by the enzyme poly(ADP-ribose) polymerase (PARP) (1, 13, 39). At the site of breakage, PARP catalyzes the transfer of the ADP-ribose moiety from its substrate, NAD+, to a limited number of protein acceptors involved in chromatin architecture and DNA metabolism, including the enzyme itself. These modified proteins, which carry long chains of negatively charged ADP-ribose polymers, lose their affinity for DNA and are thus inactivated. The short half-life of the polymer is attributed to the high activity of poly(ADP-ribose) glycohydrolase, which cleaves the ribose-ribose bond (28, 30). Therefore, poly(ADP-ribosylation) is an immediate but transient postranslational modification of nuclear proteins, induced by DNA-damaging agents. The physiological role of PARP has been much debated in the last decade, but recent molecular and genetic approaches, including expression of either a dominant-negative mutant (26, 36, 44) or antisense oligonucleotides (14), have clearly implicated PARP in the base excision repair (BER) pathway. A more definitive assessment of PARP function was recently provided by the generation of PARP-deficient mice by homologous recombination (35, 53). We found that PARP−/− mice are hypersensitive to monofunctional alkylating agents and γ-irradiation and display a marked genomic instability (sister chromatid exchanges and chromatid and chromosome breaks) following DNA damage (35). Interestingly, γ-irradiation of these mice causes acute toxicity of the epithelia of their small intestines (35), as has been observed with other DNA damage and signalling and repair enzyme deficiencies (2, 3), thus emphasizing the crucial function of DNA surveillance programs of rapidly dividing cells. Similar results indicating that PARP is important for the maintenance of genomic stability following environmental or experimental stress were recently obtained (54). In this work, we have used the two-hybrid system to identify genes encoding proteins that putatively interact with PARP and are involved in its biological function. The human PARP cDNA fused to the LexA-encoding DNA-binding domain (DBD) was used as bait to screen a HeLa cDNA library fused with the activation domain of Gal4. This screening resulted in the identification of the BER pathway protein XRCC1 (X-ray repair cross-complementing 1) as a factor that associates with PARP. This interaction was further confirmed by in vivo experiments with glutathione S-transferase (GST)-tagged fusion proteins expressed in Cos-7 and HeLa cells. XRCC1 and PARP were found to interact via their respective BRCT (BRCA1 C terminus) modules (4, 9) and via an additional site located in the N-terminal zinc-finger domain of PARP. This association dramatically decreased the catalytic activity of PARP without modifying its nick sensor function. Therefore, the association of PARP with XRCC1, a partner of DNA ligase III (7, 8) and DNA polymerase β (25), is suggestive of a role in the detection and protection of a DNA strand break and the subsequent targeting of a BER complex to the damaged site.

Journal ArticleDOI
TL;DR: For example, this paper showed that the most active thrusts usually break the ground many kilometres north of the range-fronts, along the northeast limbs of growing, asymmetric ramp-anticlines.
Abstract: Fieldwork complemented by SPOT image analysis throws light on current crustal shortening processes in the ranges of northeastern Tibet (Gansu and Qinghai provinces, China). The ongoing deformation of Late-Pleistocene bajada aprons in the forelands of the ranges involves folding, at various scales, and chiefly north-vergent, seismogenic thrusts. The most active thrusts usually break the ground many kilometres north of the range-fronts, along the northeast limbs of growing, asymmetric ramp-anticlines. Normal faulting at the apex of other growing anticlines, between the range fronts and the thrust breaks, implies slip on blind ramps connecting distinct active decollement levels that deepen southwards. The various patterns of uplift of the bajada surfaces can be used to constrain plausible links between contemporary thrusts downsection. Typically, the foreland thrusts and decollements appear to splay from master thrusts that plunge at least 15–20 km down beneath the high ranges. Plio-Quaternary anticlinal ridges rising to more than 3000 m a.s.l. expose Palaeozoic metamorphic basement in their core. In general, the geology and topography of the ranges and forelands imply that structural reliefs of the order of 5–10 km have accrued at rates of 1–2 mm yr−1 in approximately the last 5 Ma. From hill to range size, the elongated reliefs that result from such Late-Cenozoic, NE–SW shortening appear to follow a simple scaling law, with roughly constant length/width ratio, suggesting that they have grown self-similarly. The greatest mountain ranges, which are over 5.5 km high, tens of kilometres wide and hundreds of kilometres long may thus be interpreted to have formed as NW-trending ramp anticlines, at the scale of the middle–upper crust. The fairly regular, large-scale arrangement of those ranges, with parallel crests separated by piggy-back basins, the coevality of many parallel, south-dipping thrusts, and a change in the scaling ratio (from ≈5 to 8) for range widths greater than ≈30 km further suggests that they developed as a result of the northeastward migration of large thrust ramps above a broad decollement dipping SW at a shallow angle in the middle–lower crust. This, in turn, suggests that the 400–500 km-wide crustal wedge that forms the northeastern edge of the Tibet–Qinghai plateau shortens and thickens as a thick-skinned accretionary prism decoupled from the stronger upper mantle underneath. Such a thickening process must have been coupled with propagation of the Altyn Tagh fault towards the ENE because most thrust traces merge northwestwards with active branches of this fault, after veering clockwise. This process appears to typify the manner in which the Tibet–Qinghai highlands have expanded their surface area in the Neogene. The present topography and structure imply that, during much of that period, the Tibet plateau grew predominantly towards the northeast or east-northeast, but only marginally towards the north-northwest. This was accomplished by the rise, in fairly fast succession, of the Arka Tagh, Qiman Tagh, Mahan shan, Tanghenan Shan, and other NW-trending mountain ranges splaying southeastwards from the Altyn Tagh, isolating the Aqqik-Ayakkum Kol, Qaidam, Suhai and other catchments and basins that became incorporated into the highland mass as intermontane troughs. The tectonic cut-off of catchments and the ultimate infilling of basins by debris from the adjacent ranges, a result of tectonically forced internal drainage, have thus been essential relief-smoothing factors, yielding the outstandingly flat topography that makes Tibet a plateau. Using Late-Mesozoic and Neogene horizons as markers, the retrodeformation of sections across the West Qilian Ranges and Qaidam basin implies at least ≈150 km of N30°E Neogene shortening. On a broader scale, taking erosion into account, and assuming isostatic compensation and an initial crustal thickness comparable to that of the Gobi platform (47.5±5 km), minimum amounts of Late-Cenozoic crustal shortening on NE sections between the Kunlun fault and the Hexi corridor are estimated to range between 100 and 200 km. In keeping with the inference of a deep crustal decollement and with the existence of Mid-Miocene to Pliocene plutonism and volcanism south of the Kunlun range, such values suggest that the lithospheric mantle of the Qaidam plunged obliquely into the asthenosphere south of that range to minimum depths of the order of 200–300 km. A minimum of ≈150 km of shortening in the last ≈10 Ma, consistent with the average age of the earliest volcanic–plutonic rocks just south of the Kunlun (≈10.8 Ma) would imply average Late-Cenozoic rates of shortening and regional uplift in NE Tibet of at least ≈15 mm yr−1 and ≈0.2 mm yr−1, respectively. Such numbers are consistent with a cumulative sinistral offset and slip rate of at least ≈200 km and ≈2 cm yr−1, respectively, on the Altyn Tagh fault east of 88°E. The fault may have propagated more than 1000 km, to 102°E, in the last 10 Ma. Our study of ongoing tectonics in northeast Tibet is consistent with a scenario in which, while the Himalayas-Gangdese essentially ‘stagnated’ above India’s subducting mantle, much of Tibet grew by thickening of the Asian crust, as propagation of large, lithospheric, strike-slip shear zones caused the opposite edge of the plateau to migrate far into Asia. The Asian lithospheric mantle, decoupled from the crust, appears to have subducted southwards along the two Mesozoic sutures that cut Tibet north of the Gangdese, rather than to have thickened. The Bangong-Nujiang suture was probably reactivated earlier than the Jinsha-Kunlun suture, located farther north. Overall, the large-scale deformation bears a resemblance to plate tectonics at obliquely convergent margins, including slip-partioning along large strike-slip faults such as the Altyn Tagh and Kunlun faults. Simple mechanisms at the level of the lithospheric mantle are merely hidden by the broader distribution and greater complexity of strain in the crust.

Journal ArticleDOI
TL;DR: In this paper, the authors mainly focused on the hydrogenation of α, β-unsaturated aldehydes into the corresponding unsaturated alcohols and showed that when a substituent is present on the carbon atom of the carbonyl group (i.e. with ketones), there is no chance to hydrogenate selectively the C═O bond, and saturated ketones are obtained with a high yield.
Abstract: The synthesis of a large number of fine chemicals, particularly in the field of flavor and fragrance chemistry [1,2] and pharmaceuticals [3], involves the selective hydrogenation of unsaturated carbonyl intermediates as a critical step. The hydrogenation of α,β-unsaturated carbonyls into saturated carbonyls is comparatively easy to achieve because thermodynamics favor the hydro-genation of the C═C bonds; therefore, research efforts were more directed at improving the selectivity to unsaturated alcohols. When a substituent is present on the carbon atom of the carbonyl group (i.e. with ketones), there is no chance to hydrogenate selectively the C═O bond, and saturated ketones are obtained with a high yield. This review is thus mostly restricted to the hydrogenation of α, β-unsaturated aldehydes into the corresponding unsaturated alcohols.

Journal ArticleDOI
TL;DR: The unexpected properties of penetratins, a class of peptides with translocating properties and capable of carrying hydrophilic compounds across the plasma membrane, are summarized, allowing direct targeting of oligopeptides and oligonucleotides to the cytoplasm and nucleus.

Journal ArticleDOI
TL;DR: The implication of mitochondria in apoptosis has important consequences for the understanding of the normal physiology of apoptosis, its deregulation in cancer and degenerative diseases, and the development of novel cytotoxic and cytoprotective drugs.

Journal ArticleDOI
29 Jan 1998-Nature
TL;DR: Analysis of the sequence revealed an average gene density of one gene every 4.8 kilobases, and 54% of the predicted genes had significant similarity to known genes, and other interesting features were found, such as the sequence of a disease-resistance gene locus, the distribution of retroelements, and the frequent occurrence of clustered gene families.
Abstract: The plant Arabidopsis thaliana (Arabidopsis) has become an important model species for the study of many aspects of plant biology. The relatively small size of the nuclear genome and the availability of extensive physical maps of the five chromosomes provide a feasible basis for initiating sequencing of the five chromosomes. The YAC (yeast artificial chromosome)-based physical map of chromosome 4 was used to construct a sequence-ready map of cosmid and BAC (bacterial artificial chromosome) clones covering a 1.9-megabase (Mb) contiguous region, and the sequence of this region is reported here. Analysis of the sequence revealed an average gene density of one gene every 4.8 kilobases (kb), and 54% of the predicted genes had significant similarity to known genes. Other interesting features were found, such as the sequence of a disease-resistance gene locus, the distribution of retroelements, the frequent occurrence of clustered gene families, and the sequence of several classes of genes not previously encountered in plants.

Journal ArticleDOI
TL;DR: Especially in the field of enantioselective synthesis, vicinal diamines (1,2-diamines) 1 and compounds easily prepared from them are widely used by organic chemists and various strategies have been developed to produce these compounds selectively.
Abstract: Especially in the field of enantioselective synthesis, vicinal diamines (1,2-diamines) 1 and compounds easily prepared from them-such as 1,2-bisimines, 1,2-diamides, or imidazolidin-2-ones-are widely used by organic chemists. Various strategies have been developed to produce these compounds selectively. Many natural products and medicinal agents also contain a 1,2-diamino unit.

Journal ArticleDOI
TL;DR: It is argued that caspases might have a dual function in the apoptotic process: first, as signal-transduction molecules that act as facultative inducers of mitochondrial membrane changes, and, second, as processing enzymes that orchestrate the apoptosis phenotype.

Journal ArticleDOI
20 Aug 1998-Nature
TL;DR: A comparison of the global atmospheric concentration of methane as recorded in ice cores from Antarctica and Greenland permits a determination of the phase relationship (in leads or lags) of these temperature variations as mentioned in this paper.
Abstract: A central issue in climate dynamics is to understand how the Northern and Southern hemispheres are coupled during climate events. The strongest of the fast temperature changes observed in Greenland (so-called Dansgaard–Oeschger events) during the last glaciation have an analogue in the temperature record from Antarctica. A comparison of the global atmospheric concentration of methane as recorded in ice cores from Antarctica and Greenland permits a determination of the phase relationship (in leads or lags) of these temperature variations. Greenland warming events around 36 and 45 kyr before present lag their Antarctic counterpart by more than 1 kyr. On average, Antarctic climate change leads that of Greenland by 1–2.5 kyr over the period 47–23 kyr before present.

Journal ArticleDOI
TL;DR: A quasi-inertial reference frame is defined based on the radio positions of 212 extragalactic sources distributed over the entire sky as discussed by the authors, which is better than about 1 mas in both coordinates.
Abstract: A quasi-inertial reference frame is defined based on the radio positions of 212 extragalactic sources distributed over the entire sky. The positional accuracy of these sources is better than about 1 mas in both coordinates. The radio positions are based upon a general solution for all applicable dual-frequency 2.3 and 8.4 GHz Mark III very long baseline interferometry data available through the middle of 1995, consisting of 1.6 million pairs of group delay and phase delay rate observations. Positions and details are also given for an additional 396 objects that either need further observation or are currently unsuitable for the definition of a high-accuracy reference frame. The final orientation of the frame axes has been obtained by a rotation of the positions into the system of the International Celestial Reference System and is consistent with the FK5 J2000.0 optical system, within the limits of the link accuracy. The resulting International Celestial Reference Frame has been adopted by the International Astronomical Union as the fundamental celestial reference frame, replacing the FK5 optical frame as of 1998 January 1.

Journal ArticleDOI
TL;DR: The results confirm and extend recent reports indicating that the Notch receptor exists at the plasma membrane as a heterodimeric molecule, but disagree as to the nature of the protease that is responsible for the cleavage that takes place in the extracellular region.
Abstract: The Notch receptor, which is involved in numerous cell fate decisions in invertebrates and vertebrates, is synthesized as a 300-kDa precursor molecule (p300). We show here that proteolytic processing of p300 is an essential step in the formation of the biologically active receptor because only the cleaved fragments are present at the cell surface. Our results confirm and extend recent reports indicating that the Notch receptor exists at the plasma membrane as a heterodimeric molecule, but disagree as to the nature of the protease that is responsible for the cleavage that takes place in the extracellular region. We report here that constitutive processing of murine Notch1 involves a furin-like convertase. We show that the calcium ionophore A23187 and the α1-antitrypsin variant, α 1-PDX, a known inhibitor of furin-like convertases, inhibit p300 processing. When expressed in the furin-deficient Lovo cell line, p300 is not processed. In vitro digestion of a recombinant Notch-derived substrate with purified furin allowed mapping of the processing site to the carboxyl side of the sequence RQRR (amino acids 1651–1654). Mutation of these four amino acids (and of two secondary dibasic furin sites located nearby) completely abolished processing of the Notch1 receptor.

Journal ArticleDOI
TL;DR: This survey describes the molecular signals in tRNAs that trigger specific aminoacylations, and shows that alternate identity sets can be recognized by a single synthetase, and emphasize the importance of tRNA architecture and anti-determinants preventing false recognition.
Abstract: Correct expression of the genetic code at translation is directly correlated with tRNA identity. This survey describes the molecular signals in tRNAs that trigger specific aminoacylations. For most tRNAs, determinants are located at the two distal extremities: the anticodon loop and the amino acid accepting stem. In a few tRNAs, however, major identity signals are found in the core of the molecule. Identity elements have different strengths, often depend more on k cat effects than on K m effects and exhibit additive, cooperative or anti-cooperative interplay. Most determinants are in direct contact with cognate synthetases, and chemical groups on bases or ribose moieties that make functional interactions have been identified in several systems. Major determinants are conserved in evolution; however, the mechanisms by which they are expressed are species dependent. Recent studies show that alternate identity sets can be recognized by a single synthetase, and emphasize the importance of tRNA architecture and anti-determinants preventing false recognition. Identity rules apply to tRNA-like molecules and to minimalist tRNAs. Knowledge of these rules allows the manipulation of identity elements and engineering of tRNAs with switched, altered or multiple specificities.

Journal ArticleDOI
TL;DR: In this paper, a spin-glass-like transition was found in magnetic nanoparticles, with a very high surface to volume ratio, exhibiting both strong exchange anisotropy and magnetic training effect.
Abstract: $\ensuremath{\gamma}\ensuremath{-}{\mathrm{Fe}}_{2}{\mathrm{O}}_{3}$ magnetic nanoparticles, with a very high surface to volume ratio, exhibit both strong exchange anisotropy and magnetic training effect. At the same time high field irreversibility in $M\left(H\right)$ curves and zero field cooled--field cooled (ZFC-FC) processes has also been detected. A low temperature spin-glass-like transition is evidenced at ${T}_{F}\ensuremath{\approx}42\mathrm{K}$ with strong irreversibility even at $H\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}55\mathrm{kOe}$. ${T}_{F}\left(H\right)$ evolves following the well known de Almeida--Thouless line $\ensuremath{\delta}{T}_{F}\ensuremath{\propto}{H}^{2/3}$. The thermal dependence of the exchange anisotropy field ${H}_{E}$ is described by the random-field model of exchange anisotropy. In the framework of this theory, a surface spin-glass layer about 0.6 nm thick is determined.

Journal ArticleDOI
TL;DR: PARP−/− cells are extremely sensitive to apoptosis induced by triggers (like alkylating agents), which activates the base excision repair pathway of DNA, and the cleavage of PARP during apoptosis facilitates cellular disassembly and ensures the completion and irreversibility of the process.