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Biomedical subjects

F Rouyer

Publications and source records attributed to F Rouyer.

At least 19 recordsLinked to original sources

Speeding to a stop: the finite-time singularity of a spinning disk.

The final stages of a coin spinning on a flat surface have recently been proposed [H.K. Moffatt, Nature (London) 404, 833 (2000)] as an example of a finite-time singularity, wherein the precession rate of the symmetry axis of the coin diverges as it comes to a stop. We report measurements by high-speed video imaging of the rolling motion of disks and rings on a variety of surfaces. We find that the precession rate, Omega, diverges as a power law in time: Omega(t) proportional, variant (t-t(o))(-1/n), where t(o) is the instant the motion ceases. The exponent n varies between 2.7 and 3.2 under different experimental conditions. The value of n, as well as the systematic dependence of precession rate on coefficients of friction, establishes that the primary mechanism of energy dissipation is rolling friction rather than air drag, as previously suggested.

Journal Article↗

Defining the role of Drosophila lateral neurons in the control of circadian rhythms in motor activity and eclosion by targeted genetic ablation and PERIOD protein overexpression.

The ventral lateral neurons (LNvs) of the Drosophila brain that express the period (per) and pigment dispersing factor (pdf) genes play a major role in the control of circadian activity rhythms. A new P-gal4 enhancer trap line is described that is mostly expressed in the LNvs This P-gal4 line was used to ablate the LNvs by using the pro-apoptosis gene bax, to stop PER protein oscillations by overexpressing per and to block synaptic transmission with the tetanus toxin light chain (TeTxLC). Genetic ablation of these clock cells leads to the loss of robust 24-h activity rhythms and reveals a phase advance in light-dark conditions as well as a weak short-period rhythm in constant darkness. This behavioural phenotype is similar to that described for disconnected1 (disco1) mutants, in which we show that the majority of the individuals have a reduced number of dorsally projecting lateral neurons which, however, fail to express PER. In both LNv-ablated and disco1 flies, PER cycles in the so-called dorsal neurons (DNs) of the superior protocerebrum, suggesting that the weak short-period rhythm could stem from these PDF-negative cells. The overexpression of per in LNs suppresses PER protein oscillations and leads to the disruption of both activity and eclosion rhythms, indicating that PER cycling in these cells is required for both of these rhythmic behaviours. Interestingly, flies overexpressing PER in the LNs do not show any weak short-period rhythms, although PER cycles in at least a fraction of the DNs, suggesting a dominant role of the LNs on the behavioural rhythms. Expression of TeTxLC in the LNvs does not impair activity rhythms, which indicates that the PDF-expressing neurons do not use synaptobrevin-dependent transmission to control these rhythms.

Animals↗

Velocity fluctuations in a homogeneous 2D granular gas in steady state

We have measured the spectrum of velocity fluctuations in a granular system confined to a vertical plane and driven into a homogeneous, steady state by strong vertical vibration. The distribution of horizontal velocities is not Maxwell-Boltzmann and is given by P(v) = Cexp[-beta(|v|/sigma)(alpha)] where alpha = 1.55+/-0.1 at all frequencies and amplitudes investigated, and also for varying boundary conditions. The deviation from Maxwell-Boltzmann statistics occurs in the absence of spatial clustering and does not result from an inhomogeneous average over regions of varying local density. Surprisingly, P(v) has the same shape over a wide range of densities.

Journal Article↗

Genetic and developmental models for the neural control of breathing in vertebrates.

The present paper reviews some of the possible mechanisms that may link gene function in the brainstem and breathing patterns in vertebrates. On one hand, adaptation and acclimatisation of mature breathing to environmental constraints such as hypoxia, involves complex regulation of the gene expression in precise cardiorespiratory sites of the brainstem. On the other hand, targeted inactivation of different genes suggests that postnatal respiratory variables at rest depend on genes controlling the prenatal development of the brainstem. During embryogenesis, neurotrophins (gdnf, bdnf) regulate the survival of specific cellular populations composing the respiratory neuronal network. The expression of developmental genes such as Hox and Krox-20 initiates hindbrain segmentation, the earliest sign of regionalisation in the brainstem. As shown in the chick embryo, segmental specifications allow the establishment of an active embryonic rhythmic network and later insertion of specific neuronal circuits increasing the primordial rhythm frequency to near mature values.

Aging↗

Effects of circadian mutations and LD periodicity on the life span of Drosophila melanogaster.

The pervasive occurrence of circadian clocks throughout the living world underlines their adaptive value. Nonetheless, there is surprisingly little evidence for a negative impact, on any animal species, of a constant discrepancy between the environmental and endogenous periods. Male Drosophila melanogaster per mutants with altered circadian periods were compared to the wild type in two different LD schedules. Life span was used as a global index of physiological adaptation. The life span of the mutants was significantly reduced by up to 15% for the flies whose period differs most from that of the wild type. A reduction was observed even when flies were kept in an LD schedule fitting a mutant period. The LD schedule made no significant difference on its own, but the authors found evidence for an interaction between genotype and LD schedule in determining life span. These results are consistent with the importance of the circadian clock in maintaining internal temporal order independent of environmental cycles. Nonetheless, a large difference between the environmental and endogenous periods has a measurable impact.

Alleles↗

A new gene encoding a putative transcription factor regulated by the Drosophila circadian clock.

Circadian rhythms of locomotor activity and eclosion in Drosophila depend upon the reciprocal autoregulation of the period (per) and timeless (tim) genes. As part of this regulatory loop, per and tim mRNA levels oscillate in a circadian fashion. Other cycling transcripts may participate in this central pacemaker mechanism or represent outputs of the clock. In this paper, we report the isolation of Crg-1, a new circadianly regulated gene. Like per and tim transcript levels, Crg-1 transcript levels oscillate with a 24 h period in light:dark (LD) conditions, with a maximal abundance at the beginning of the night. These oscillations persist in complete darkness and depend upon per and tim proteins. The putative CRG-1 proteins show some sequence similarity with the DNA-binding domain of the HNF3/fork head family of transcription factors. In the adult head, in situ hybridization analysis reveals that per and Crg-1 have similar expression patterns in the eyes and optic lobes.

Alternative Splicing↗

Analysis of period circadian expression in the Drosophila head by in situ hybridization.

The expression of the period (per) gene of Drosophila melanogaster has been studied by in situ hybridization in the adult's head, where it is required for the fly to exhibit behavioral circadian rhythms. We have used non-radioactive in situ hybridization to obtain a high sensitivity and specificity on head sections, with single cell resolution. Consistent with previous per protein- or per reporter gene-expression, per-expressing cells were detected in the optic lobes and the central brain, as well as in the head sensory organs: eyes, ocelli, maxillary palps and proboscis. In the brain and the eyes, circadian fluctuations of the per mRNA abundance were observed in different per expressing cells.

Animals↗

Members of a family of Drosophila putative odorant-binding proteins are expressed in different subsets of olfactory hairs.

A polymerase chain reaction-based method was used to generate a Drosophila melanogaster antennal cDNA library from which head cDNAs were subtracted. We identified five cDNAs that code for antennal proteins containing six cysteines in a conserved pattern shared with known moth antennal proteins, including pheromone-binding proteins. Another cDNA codes for a protein related to vertebrate brain proteins that bind hydrophobic ligands. In all, we describe seven antennal proteins which contain potential signal peptides, suggesting that, like pheromone-binding proteins, they may be secreted in the lumen of olfactory hairs. The expression patterns of these putative odorant-binding proteins define at least four different subsets of olfactory hairs and suggest that the Drosophila olfactory apparatus is functionally segregated.

Amino Acid Sequence↗

An interspersed repeated sequence specific for human subtelomeric regions.

A family of DNA loci (DNF28) from the pseudoautosomal region of the human sex chromosomes is characterized by a repeated element (STIR: subtelomeric interspersed repeat) which detects homologous sequences in the telomeric regions of human autosomes by in situ hybridization. Several STIR elements from both the pseudoautosomal region and terminal parts of autosomes were cloned and sequenced. A conserved 350 bp sequence and some characteristic structural differences between the autosomal and pseudoautosomal STIRs were observed. Screening of the DNA sequence databases with a consensus sequence revealed the presence of STIRs in several human loci localized in the terminal parts of different chromosomes. We mapped single copy probes flanking the cloned autosomal STIRs to the subtelomeric parts of six different chromosomes by in situ hybridization and genetic linkage analysis. The linkage data show a greatly increased recombination frequency in the subtelomeric regions of the chromosomes, especially in male meiosis. The STIR elements, specifically located in subtelomeric regions, could play a role in the peculiar recombination properties of these chromosomal regions, e.g. by promoting initiation of pairing at meiosis.

Amino Acid Sequence↗

Isolation of sequences from Xp22.3 and deletion mapping using sex chromosome rearrangements from human X-Y interchange sex reversals.

A repeated DNA element (STIR) interspersed in Xp22.3 and on the Y chromosome has been used as a tag to isolate seven single-copy probes from the human sex chromosomes. The seven probes detect X-specific loci located in Xp22.3. Using a panel of X-chromosomal deletions from X-Y interchange sex reversals (XX males and XY females), these X-specific loci and some additional ones were mapped to four contiguous intervals of Xp22.3, proximal to the pseudoautosomal region and distal to STS. The construction of this deletion map of the terminal part of the human X chromosome can serve as a starting point for a long-range physical map of Xp22.3 and for a more accurate mapping of genetic diseases located in Xp22.3.

Animals↗

[The Y chromosome and sex determination].

The structure and function of the human Y chromosome have been approached by molecular genetics. The use of Y-derived DNA probes to analyze the Y chromosome of patients with sexual differentiation abnormalities allowed the construction of a deletion map localizing TDF (testis determining factor) in the terminal part of the short arm. These studies culminated recently in the isolation of a candidate gene for the TDF locus. Nevertheless, the existence of a related locus on the X chromosome does not fit with the simple hypothesis of a single Y-located gene for testis differentiation. The finding of a strictly homologous region at the tip of the short arms of X and Y chromosomes allowed the characterization of another major property of the sex chromosomes. These so called pseudoautosomal DNA sequences show only a partial sex linkage and can be exchanged between X and Y chromosomes during male meiosis. Genetic analysis and determination of the physical length of the pseudoautosomal region show that it is subjected in male meiosis, to a recombination rate about 20 times higher than the mean value of the human genome. In 1966, Ferguson-Smith proposed that an abnormal cross-over was responsible for both types of sex inversions in humans: XX males and XY females. Segregation analysis of the pseudoautosomal loci in these patients has demonstrated the validity of this hypothesis and shown the existence of sex inversions unrelated to the TDF locus. The construction of a detailed map of the human Y chromosome enables the search for new genes (H-Y antigen, fertility gene(s]. The finding of several homologous regions on the sex chromosomes confirms the hypothesis of a common origin and should help to understand the establishment of sex determination and X inactivation mechanisms during mammalian evolution.

Chromosome Deletion↗

A sex chromosome rearrangement in a human XX male caused by Alu-Alu recombination.

Human XX maleness is often due to the presence of Y-specific DNA, resulting from abnormal interchange of terminal parts of the short arms of the X and Y chromosomes. In an XX male, a rearrangement is observed at locus DXYS5, the most proximal Yp locus detected in this patient. Cloning and analysis of the rearranged DNA fragment revealed pseudoautosomal sequences located beyond the breakpoint. We propose that this XX male arose by abnormal crossing over between DXYS5 on the Y chromosome and a pseudoautosomal locus on the X chromosome during paternal meiosis. Sequence analysis of the junction shows that homologous recombination occurred between two Alu sequences from these otherwise nonhomologous regions. The site of recombination is localized to the putative transcription promoter region of the Alu sequences.

Cells, Cultured↗

Two highly polymorphic minisatellites from the pseudoautosomal region of the human sex chromosomes.

Two pseudoautosomal loci DXYS15 and DXYS17 from the pairing region of the human sex chromosomes display a high variability with at least eight alleles each. The structural elements responsible for the polymorphisms have been isolated and sequenced. In both cases the variations result from DNA rearrangements occurring in tandemly repeated sequences (minisatellites) of 21-29 nucleotides for DXYS15 and 28-33 nucleotides for DXYS17. At reduced stringency, the DXYS15 minisatellite detects other hypervariable sequences located in other parts of the genome and hence represents a new family of minisatellites. In contrast to most other known hypervariable families, the DXYS15 hypervariable sequence displays a very high AT content.

Alleles↗