Showing papers by "Collège de France published in 2002"

Toward Self-Organization and Complex Matter

Abstract: Beyond molecular chemistry based on the covalent bond, supramolecular chemistry aims at developing highly complex chemical systems from components interacting through noncovalent intermolecular forces. Over the past quarter century, supramolecular chemistry has grown into a major field and has fueled numerous developments at the interfaces with biology and physics. Some of the conceptual advances and future challenges are profiled here.

Contact time of a bouncing drop

Abstract: When a liquid drop lands on a solid surface without wetting it, it bounces with remarkable elasticity. Here we measure how long the drop remains in contact with the solid during the shock, a problem that was considered by Hertz for a bouncing ball. Our findings could help to quantify the efficiency of water-repellent surfaces (super-hydrophobic solids) and to improve water-cooling of hot solids, which is limited by the rebounding of drops as well as by temperature effects.

A new hominid from the Upper Miocene of Chad, Central Africa

Abstract: The search for the earliest fossil evidence of the human lineage has been concentrated in East Africa. Here we report the discovery of six hominid specimens from Chad, central Africa, 2,500 km from the East African Rift Valley. The fossils include a nearly complete cranium and fragmentary lower jaws. The associated fauna suggest the fossils are between 6 and 7 million years old. The fossils display a unique mosaic of primitive and derived characters, and constitute a new genus and species of hominid. The distance from the Rift Valley, and the great antiquity of the fossils, suggest that the earliest members of the hominid clade were more widely distributed than has been thought, and that the divergence between the human and chimpanzee lineages was earlier than indicated by most molecular studies. From their initial description in 1925 1 until 1995, hominids from the Pliocene (5.3‐1.6 million years, Myr) and late Upper Miocene (,7.5‐5.3 Myr) were known only from southern and eastern Africa. This distribution led some authors to postulate an East African origin for the hominid clade (where the term ‘hominid’ refers to any member of that group more closely related to extant humans than to

Abnormal lymphatic vessel development in neuropilin 2 mutant mice.

Abstract: Neuropilin 2 is a receptor for class III semaphorins and for certain members of the vascular endothelial growth factor family. Targeted inactivation of the neuropilin 2 gene (Nrp2) has previously shown its role in neural development. We report that neuropilin 2 expression in the vascular system is restricted to veins and lymphatic vessels. Homozygous Nrp2 mutants show absence or severe reduction of small lymphatic vessels and capillaries during development. This correlated with a reduction of DNA synthesis in the lymphatic endothelial cells of the mutants. Arteries, veins and larger, collecting lymphatic vessels developed normally, suggesting that neuropilin 2 is selectively required for the formation of small lymphatic vessels and capillaries.

Rough ideas on wetting

Abstract: After a brief presentation of the classical laws of wetting, we review different phenomenological descriptions of rough wetting, i.e., show how these classical laws must be modified on rough solids. This introduces the questions of hemi-wicking (can a film propagate inside the texture of a solid ?), rough films (is it possible for a liquid film to follow the roughness of a solid ?) and super-hydrophobicity (how can a solid be designed to become water repellent ?).

Supramolecular polymer chemistry—scope and perspectives†‡

Abstract: The connection of molecular monomers through non-covalent intermolecular interactions leads to the formation of polymolecular entities defining a supramolecular polymer chemistry. The basic features of this field are presented and illustrated by some selected results. Thus, the molecular recognition directed association between monomers bearing complementary hydrogen bonding groups leads to linear supramolecular polymers and liquid crystals. Also, rigid rod, two-dimensional, metal coordination-based, side-chain and cross-linked supramolecular polymeric entities may be envisaged and several types have been generated. Like supramolecular materials in general, supramolecular polymers are reversible, constitutionally dynamic materials, capable of modifying their constitution by exchanging, recombining, incorporating components. They may present a variety of novel properties and behave as adaptive materials.

Interactions between Hox-negative cephalic neural crest cells and the foregut endoderm in patterning the facial skeleton in the vertebrate head.

Abstract: The vertebrate face contains bones that differentiate from mesenchymal cells of neural crest origin, which colonize the median nasofrontal bud and the first branchial arches. The patterning of individual facial bones and their relative positions occurs through mechanisms that remained elusive. During the early stages of head morphogenesis, an endodermal cul-de-sac, destined to become Sessel's pouch, underlies the nasofrontal bud. Reiterative outpocketings of the foregut then form the branchial pouches. We have tested the capacity of endoderm of the avian neurula to specify the facial skeleton by performing ablations or grafts of defined endodermal regions. Neural crest cells that do not express Hox genes respond to patterning cues produced regionally in the anterior endoderm to yield distinct skeletal components of the upper face and jaws. However, Hox-expressing neural crest cells do not respond to these cues. Bone orientation is likewise dependent on the position of the endoderm relative to the embryonic axes. Our findings thus indicate that the endoderm instructs neural crest cells as to the size, shape and position of all the facial skeletal elements, whether they are cartilage or membrane bones.

Visual-vestibular interactive responses in the macaque ventral intraparietal area (VIP).

Abstract: Self-motion detection requires the interaction of a number of sensory systems for correct perceptual interpretation of a given movement and an eventual motor response. Parietal cortical areas are thought to play an important role in this function, and we have thus studied the encoding of multimodal signals and their spatiotemporal interactions in the ventral intraparietal area of macaque monkeys. Thereby, we have identified for the first time the presence of vestibular sensory input to this area and described its interaction with somatosensory and visual signals, via extracellular single-cell recordings in awake head-fixed animals. Visual responses were driven by large field stimuli that simulated either backward or forward self-motion (contraction or expansion stimuli, respectively), or movement in the frontoparallel plane (visual increments moving simultaneously in the same direction). While the dominant sensory modality in most neurons was visual, about one third of all recorded neurons responded to horizontal rotation. These vestibular responses were typically in phase with head velocity, but in some cases they could signal acceleration or even showed integration to position. The associated visual responses were always codirectional with the vestibular on-direction, i.e. noncomplementary. Somatosensory responses were in register with the visual preferred direction, either in the same or in the opposite direction, thus signalling translation or rotation in the horizontal plane. These results, taken together with data on responses to optic flow stimuli obtained in a parallel study, strongly suggest an involvement of area VIP in the analysis and the encoding of self-motion.

Direct measurement of the Wigner function of a one-photon Fock state in a cavity.

Abstract: We have measured the complete Wigner function $W$ of the vacuum and of a single-photon state for a field stored in a high-$Q$ cavity. This experiment implements the direct Lutterbach and Davidovich method [L. G. Lutterbach and L. Davidovich, Phys. Rev. Lett. 78, 2547 (1997)] and is based on the dispersive interaction of a single circular Rydberg atom with the cavity field. The nonclassical nature of the single-photon field is exhibited by a region of negative $W$ values. Extensions to other nonclassical cavity field states are discussed.

Noncommutative Finite-Dimensional Manifolds. I. Spherical Manifolds and Related Examples

Abstract: We exhibit large classes of examples of noncommutative finite-dimensional manifolds which are (non-formal) deformations of classical manifolds. The main result of this paper is a complete description of noncommutative three-dimensional spherical manifolds, a noncommutative version of the sphere S3 defined by basic K-theoretic equations. We find a 3-parameter family of deformations \(\) of the standard 3-sphere S3 and a corresponding 3-parameter deformation of the 4-dimensional Euclidean space ℝ4. For generic values of the deformation parameters we show that the obtained algebras of polynomials on the deformed ℝ4u only depend on two parameters and are isomorphic to the algebras introduced by Sklyanin in connection with the Yang-Baxter equation. It follows that different \(\) can span the same \(\). This equivalence generates a foliation of the parameter space Σ. This foliation admits singular leaves reduced to a point. These critical points are either isolated or fall in two 1-parameter families \(\). Up to the simple operation of taking the fixed algebra by an involution, these two families are identical and we concentrate here on C+. For \(\) the above isomorphism with the Sklyanin algebra breaks down and the corresponding algebras are special cases of θ-deformations, a notion which we generalize in any dimension and various contexts, and study in some detail. Here, and this point is crucial, the dimension is not an artifact, i.e. the dimension of the classical model, but is the Hochschild dimension of the corresponding algebra which remains constant during the deformation. Besides the standard noncommutative tori, examples of θ-deformations include the recently defined noncommutative 4-sphere \(\) as well as m-dimensional generalizations, noncommutative versions of spaces \(\) and quantum groups which are deformations of various classical groups. We develop general tools such as the twisting of the Clifford algebras in order to exhibit the spherical property of the hermitian projections corresponding to the noncommutative \(\)-dimensional spherical manifolds \(\). A key result is the differential self-duality properties of these projections which generalize the self-duality of the round instanton.

On Fluid/Wall Slippage

Abstract: Certain (nonpolymeric) fluids show an anomalously low friction when flowing against well-chosen solid walls. We discuss here one possible explanation, postulating that a gaseous film of small thickness h is present between fluid and wall. When h is smaller than the mean free path l of the gas (Knudsen regime), the Navier length b is expected to be independent of h and very large (micrometers).

The Function of TIF2/GRIP1 in Mouse Reproduction Is Distinct from Those of SRC-1 and p/CIP

Abstract: Human TIF2 (hTIF2) is a member of the p160 family of nuclear receptor coactivators, which includes SRC-1 and p/CIP. Although the functions of hTIF2 and of its mouse homolog (GRIP1 or mTIF2) have been clearly established in vitro, their physiological role remains elusive. Here, we have generated mice lacking mTIF2/GRIP1 and examined their phenotype with a particular emphasis on reproductive functions. TIF2−/− mice are viable, but the fertility of both sexes is impaired. Male hypofertility is due to defects in both spermiogenesis (teratozoospermia) and age-dependent testicular degeneration, and TIF2 expression appears to be essential for adhesion of Sertoli cells to germ cells. Female hypofertility is due to a placental hypoplasia that most probably reflects a requirement for maternal TIF2 in decidua stromal cells that face the developing placenta. We conclude that TIF2 plays a critical role in mouse reproductive functions, whereas previous reports have not revealed serious fertility impairment in SRC-1−/− or p/CIP−/− mutants. Thus, even though the three p160 coactivators exhibit strong sequence homology and similar activity in assays in vitro, they play distinct physiological roles in vivo, as their genetic eliminations result in distinct pathologies.

Negative effect of Hox gene expression on the development of the neural crest-derived facial skeleton

Abstract: Diencephalic, mesencephalic and metencephalic neural crest cells are skeletogenic and derive from neural folds that do not express Hox genes. In order to examine the influence of Hox gene expression on skull morphogenesis, expression of Hoxa2, Hoxa3 and Hoxb4 in conjunction with that of the green fluorescent protein has been selectively targeted to the Hox-negative neural folds of the avian embryo prior to the onset of crest cell emigration. Hoxa2 expression precludes the development of the entire facial skeleton. Transgenic Hoxa2 embryos such as those from which the Hox-negative domain of the cephalic neural crest has been removed have no upper or lower jaws and no frontonasal structures. Embryos subjected to the forced expression of Hoxa3 and Hoxb4 show severe defects in the facial skeleton but not a complete absence of facial cartilage. Hoxa3 prevents the formation of the skeleton derived from the first branchial arch, but allows the development (albeit reduced) of the nasal septum. Hoxb4, by contrast, hampers the formation of the nasal bud-derived skeleton, while allowing that of a proximal (but not distal) segment of the lower jaw. The combined effect of Hoxa3 and Hoxb4 prevents the formation of facial skeletal structures, comparable with Hoxa2. None of these genes impairs the formation of neural derivatives of the crest. These results suggest that over the course of evolution, the absence of Hox gene expression in the anterior part of the chordate embryo was crucial in the vertebrate phylum for the development of a face, jaws and brain case, and, hence, also for that of the forebrain.

Genetic evidence that oxidative derivatives of retinoic acid are not involved in retinoid signaling during mouse development.

Abstract: Retinoic acid, the active derivative of vitamin A (retinol), is a hormonal signaling molecule that acts in developing and adult tissues1. The Cyp26a1 (cytochrome p450, 26) protein metabolizes retinoic acid into more polar hydroxylated and oxidized derivatives2,3. Whether some of these derivatives are biologically active metabolites has been debated4,5. Cyp26a1−/− mouse fetuses have lethal morphogenetic phenotypes mimicking those generated by excess retinoic acid administration, indicating that human CYP26A1 may be essential in controlling retinoic acid levels during development6,7. This hypothesis suggests that the Cyp26a1−/− phenotype could be rescued under conditions in which embryonic retinoic acid levels are decreased. We show that Cyp26a1−/− mice are phenotypically rescued by heterozygous disruption of Aldh1a2 (also known as Raldh2), which encodes a retinaldehyde dehydrogenase responsible for the synthesis of retinoic acid during early embryonic development8,9. Aldh1a2 haploinsufficiency prevents the appearance of spina bifida and rescues the development of posterior structures (sacral/caudal vertebrae, hindgut, urogenital tract), while partly preventing cervical vertebral transformations and hindbrain pattern alterations in Cyp26a1−/− mice. Thus, some of these double-mutant mice can reach adulthood. This study is the first report of a mutation acting as a dominant suppressor of a lethal morphogenetic mutation in mammals. We provide genetic evidence that ALDH1A2 and CYP26A1 activities concurrently establish local embryonic retinoic acid levels that must be finely tuned to allow posterior organ development and to prevent spina bifida.

Heading encoding in the macaque ventral intraparietal area (VIP).

Abstract: We recorded neuronal responses to optic flow stimuli in the ventral intraparietal area (VIP) of two awake macaque monkeys. According to previous studies on optic flow responses in monkey extrastriate cortex we used different stimulus classes: frontoparallel motion, radial stimuli (expansion and contraction) and rotational stimuli (clockwise and counter-clockwise). Seventy-five percent of the cells showed statistically significant responses to one or more of these optic flow stimuli. Shifting the location of the singularity of the optic flow stimuli within the visual field led to a response modulation in almost all cases. For the majority of neurons, this modulatory influence could be approximated in a statistically significant manner by a two-dimensional linear regression. Gradient directions, derived from the regression parameters and indicating the direction of the steepest increase in the responses, were uniformly distributed. At the population level, an unbiased average response for the stimuli with different focus locations was observed. By applying a population code, termed 'isofrequency encoding', we demonstrate the capability of the recorded neuronal ensemble to retrieve the focus location from its population discharge. Responses to expansion and contraction stimuli cannot be predicted based on quantitative data on a neuron's frontoparallel preferred stimulus direction and the location and size of its receptive field. These results, taken together with data on polymodal motion responses in this area, suggest an involvement of area VIP in the analysis and the encoding of heading.

Embryonic retinoic acid synthesis is required for forelimb growth and anteroposterior patterning in the mouse.

Abstract: Numerous studies, often performed on avian embryos, have implicated retinoic acid (RA) in the control of limb bud growth and patterning. Here we have investigated whether the lack of endogenous RA synthesis affects limb morphogenesis in mutant mouse embryos deficient for the retinaldehyde dehydrogenase 2 (Raldh2/Aldh1a2). These mutants, which have no detectable embryonic RA except in the developing retina, die at E9.5-E10 without any evidence of limb bud formation, but maternal RA supplementation through oral gavage from E7.5 can extend their survival. Such survivors exhibit highly reduced forelimb rudiments, but apparently normal hindlimbs. By providing RA within maternal food, we found both a stage- and dose-dependency for rescue of forelimb growth and patterning. Following RA supplementation from E7.5 to 8.5, mutant forelimbs are markedly hypoplastic and lack anteroposterior (AP) patterning, with a single medial cartilage and 1-2 digit rudiments. RA provided until E9.5 significantly rescues forelimb growth, but cannot restore normal AP patterning. Increasing the RA dose rescues the hypodactyly, but leads to lack of asymmetry of the digit pattern, with abnormally long first digit or symmetrical polydactyly. Mutant forelimb buds are characterized by lack of expression or abnormal distal distribution of Sonic hedgehog (Shh) transcripts, sometimes with highest expression anteriorly. Downregulation or ectopic anterior expression of Fgf4 is also seen. As a result, genes such as Bmp2 or Hoxd genes are expressed symmetrically along the AP axis of the forelimb buds, and/or later, of the autopod. We suggest that RA signaling cooperates with a posteriorly restricted factor such as dHand, to generate a functional zone of polarizing activity (ZPA).

Estradiol Alters Nitric Oxide Production in the Mouse Aorta Through the α-, but not β-, Estrogen Receptor

Abstract: Although estradiol (E2) has been recognized to exert several vasculoprotective effects in several species, its effects in mouse vasomotion are unknown, and consequently, so is the estrogen receptor subtype mediating these effects. We investigated the effect of E2 (80 μg/kg/day for 15 days) on NO production in the thoracic aorta of ovariectomized C57Bl/6 mice compared with those given placebo. E2 increased basal NO production. In contrast, the relaxation in response to ATP, to the calcium ionophore A23187, and to sodium nitroprusside was unaltered by E2, whereas acetylcholine-elicited relaxation was decreased. The abundance of NO synthase I, II, and III immunoreactive proteins (using Western blot) in thoracic aorta homogenates was unchanged by E2. To determine the estrogen receptor (ER) subtype involved in these effects, transgenic mice in which either the ERα or ERβ has been disrupted were ovariectomized and treated, or not, with E2. Basal NO production was increased and the sensitivity to acetylcholine decreased in ERβ knockout mice in response to E2, whereas this effect was abolished in ERα knockout mice. Finally, these effects of E2 on vasomotion required long-term and/or in vivo exposure, as short-term incubation of aortic rings with 10 nmol/L E2 in the isolated organ chamber did not elicit any vasoactive effects. In conclusion, this study demonstrates that ERα, but not ERβ, mediates the beneficial effect of E2 on basal NO production.

Lessons from constitutively active mutants of G protein-coupled receptors.

Abstract: In the past decade, the concept of constitutive activity has profoundly modified our understanding of G protein-coupled-receptors (GPCRs). Here, we review the contribution of constitutively active mutants (CAMs) to our understanding of three aspects of GPCR physiopathology: (1) GPCR activation is a complex mechanism involving both the release of inactive state conformational constraints, mimicked by most CAMs, and the creation of new interactions that stabilize the active state and are mimicked by a restricted set of CAMs; (2) GPCR phosphorylation, internalization and desensitization processes are activated by receptor conformations, which partly overlap those activating G protein; (3) natural CAMs, mostly affecting GPCRs of the endocrine system, are found in several hereditary and acquired diseases, including cancers. One major remaining question is how CAMs recapitulate the different structural modifications of the agonist-induced active conformation(s) of the wild-type receptor. This characterization is a prerequisite for further use of CAMs as ligand-free models of active GPCRs in structural, cellular and physiological studies.

Progesterone stimulates the activity of the promoters of peripheral myelin protein-22 and protein zero genes in Schwann cells.

Abstract: To understand better the mechanisms by which progesterone (PROG) promotes myelination in the PNS, cultured rat Schwann cells were transiently transfected with reporter constructs in which luciferase expression was controlled by the promoter region of either the peripheral myelin protein-22 (PMP22) or the protein zero (P0) genes. PROG stimulated the P0 promoter and promoter 1, but not promoter 2, of PMP22. The effect of PROG was specific, as estradiol and testosterone only weakly activated promoters. Dose-response curves for stimulation of both promoter constructs by PROG were biphasic. RU486, a PROG antagonist, did not abolish the effect of PROG, but stimulated promoter activities by itself. In the human carcinoma cell line T47D expressing high levels of PROG receptor, PROG did not stimulate the P0 and PMP22 promoters, whereas the promoter region of the mouse mammary tumor virus was fully activated. Thus, the activation by PROG of promoter activity of two peripheral myelin protein genes is Schwann-cell specific.