Cellular and Molecular Mechanisms Underlying srGAP2 Function During Neuronal Development

During brain development, proper neuronal migration and morphogenesis is critical for the establishment of functional neuronal circuits. I have identified that srGAP2 negatively regulates neuronal migration and induces both neurite outgrowth and branching through the ability of its F-BAR domain to induce filopodia-like membrane protrusions resembling those induced by I-BAR domains in vivo and in vitro. Previous work has suggested that in non-neuronal cells, forced expression of proteins that promote filopodia decrease the rate of cell migration and the persistence of leading edge protrusions. srGAP2 knockdown reduces leading process branching and increases the rate of neuronal migration in vivo. Overexpression of srGAP2 or its F-BAR domain has the opposite effects, increasing leading process branching and dynamics and blocking migration. Finally, expression of a truncated form of the F-BAR domain that localizes to the membrane but fails to elicit filopodia-like membrane protrusions does not inhibit neuronal migration. This work highlights the functional importance of proteins directly regulating membrane deformation for proper neuronal migration and morphogenesis

A New Type of Electron Nuclear-Spin Interaction from Resistively Detected NMR in the Fractional Quantum Hall Effect Regime

Two dimensional electron gases in narrow GaAs quantum wells show huge longitudinal resistance (HLR) values at certain fractional filling factors. Applying an RF field with frequencies corresponding to the nuclear spin splittings of {69}Ga, {71}Ga and {75}As leads to a substantial decreases of the HLR establishing a novel type of resistively detected NMR. These resonances are split into four sub lines each. Neither the number of sub lines nor the size of the splitting can be explained by established interaction mechanisms.Comment: 4 pages, 3 figure

Inhibition of Expression in Escherichia coli of a Virulence Regulator MglB of Francisella tularensis Using External Guide Sequence Technology

External guide sequences (EGSs) have successfully been used to inhibit expression of target genes at the post-transcriptional level in both prokaryotes and eukaryotes. We previously reported that EGS accessible and cleavable sites in the target RNAs can rapidly be identified by screening random EGS (rEGS) libraries. Here the method of screening rEGS libraries and a partial RNase T1 digestion assay were used to identify sites accessible to EGSs in the mRNA of a global virulence regulator MglB from Francisella tularensis, a Gram-negative pathogenic bacterium. Specific EGSs were subsequently designed and their activities in terms of the cleavage of mglB mRNA by RNase P were tested in vitro and in vivo. EGS73, EGS148, and EGS155 in both stem and M1 EGS constructs induced mglB mRNA cleavage in vitro. Expression of stem EGS73 and EGS155 in Escherichia coli resulted in significant reduction of the mglB mRNA level coded for the F. tularensis mglB gene inserted in those cells

The origin of life: chemical evolution of a metabolic system in a mineral honeycomb?

For the RNA-world hypothesis to be ecologically feasible, selection mechanisms acting on replicator communities need to be invoked and the corresponding scenarios of molecular evolution specified. Complementing our previous models of chemical evolution on mineral surfaces, in which selection was the consequence of the limited mobility of macromolecules attached to the surface, here we offer an alternative realization of prebiotic group-level selection: the physical encapsulation of local replicator communities into the pores of the mineral substrate. Based on cellular automaton simulations we argue that the effect of group selection in a mineral honeycomb could have been efficient enough to keep prebiotic ribozymes of different specificities and replication rates coexistent, and their metabolic cooperation protected from extensive molecular parasitism. We suggest that mutants of the mild parasites persistent in the metabolic system can acquire useful functions such as replicase activity or the production of membrane components, thus opening the way for the evolution of the first autonomous protocells on Earth

<i>Gaia</i> Data Release 1. Summary of the astrometric, photometric, and survey properties

Context. At about 1000 days after the launch of Gaia we present the first Gaia data release, Gaia DR1, consisting of astrometry and photometry for over 1 billion sources brighter than magnitude 20.7. Aims. A summary of Gaia DR1 is presented along with illustrations of the scientific quality of the data, followed by a discussion of the limitations due to the preliminary nature of this release. Methods. The raw data collected by Gaia during the first 14 months of the mission have been processed by the Gaia Data Processing and Analysis Consortium (DPAC) and turned into an astrometric and photometric catalogue. Results. Gaia DR1 consists of three components: a primary astrometric data set which contains the positions, parallaxes, and mean proper motions for about 2 million of the brightest stars in common with the HIPPARCOS and Tycho-2 catalogues – a realisation of the Tycho-Gaia Astrometric Solution (TGAS) – and a secondary astrometric data set containing the positions for an additional 1.1 billion sources. The second component is the photometric data set, consisting of mean G-band magnitudes for all sources. The G-band light curves and the characteristics of ∼3000 Cepheid and RR-Lyrae stars, observed at high cadence around the south ecliptic pole, form the third component. For the primary astrometric data set the typical uncertainty is about 0.3 mas for the positions and parallaxes, and about 1 mas yr−1 for the proper motions. A systematic component of ∼0.3 mas should be added to the parallax uncertainties. For the subset of ∼94 000 HIPPARCOS stars in the primary data set, the proper motions are much more precise at about 0.06 mas yr−1. For the secondary astrometric data set, the typical uncertainty of the positions is ∼10 mas. The median uncertainties on the mean G-band magnitudes range from the mmag level to ∼0.03 mag over the magnitude range 5 to 20.7. Conclusions. Gaia DR1 is an important milestone ahead of the next Gaia data release, which will feature five-parameter astrometry for all sources. Extensive validation shows that Gaia DR1 represents a major advance in the mapping of the heavens and the availability of basic stellar data that underpin observational astrophysics. Nevertheless, the very preliminary nature of this first Gaia data release does lead to a number of important limitations to the data quality which should be carefully considered before drawing conclusions from the data

High Abundance Proteins Depletion vs Low Abundance Proteins Enrichment: Comparison of Methods to Reduce the Plasma Proteome Complexity

BACKGROUND: To date, the complexity of the plasma proteome exceeds the analytical capacity of conventional approaches to isolate lower abundance proteins that may prove to be informative biomarkers. Only complex multistep separation strategies have been able to detect a substantial number of low abundance proteins (<100 ng/ml). The first step of these protocols is generally the depletion of high abundance proteins by the use of immunoaffinity columns or, alternatively, the enrichment of by the use of solid phase hexapeptides ligand libraries. METHODOLOGY/PRINCIPAL FINDINGS: Here we present a direct comparison of these two approaches. Following either approach, the plasma sample was further fractionated by SCX chromatography and analyzed by RP-LC-MS/MS with a Q-TOF mass spectrometer. The depletion of the 20 most abundant plasma proteins allowed the identification of about 25% more proteins than those detectable following low abundance proteins enrichment. The two datasets are partially overlapping and the identified proteins belong to the same order of magnitude in terms of plasma concentration. CONCLUSIONS/SIGNIFICANCE: Our results show that the two approaches give complementary results. However, the enrichment of low abundance proteins has the great advantage of obtaining much larger amount of material that can be used for further fractionations and analyses and emerges also as a cheaper and technically simpler approach. Collectively, these data indicate that the enrichment approach seems more suitable as the first stage of a complex multi-step fractionation protocol

Gaia Data Release 3: G_RVS photometry from the RVS spectra

Gaia Data Release 3 (DR3) contains the first release of magnitudes estimated from the integration of Radial Velocity Spectrometer (RVS) spectra for a sample of about 32.2 million stars brighter than G_RVS~14 mag (or G~15 mag). In this paper, we describe the data used and the approach adopted to derive and validate the G_RVS magnitudes published in DR3. We also provide estimates of the G_RVS passband and associated G_RVS zero-point. We derived G_RVS photometry from the integration of RVS spectra over the wavelength range from 846 to 870 nm. We processed these spectra following a procedure similar to that used for DR2, but incorporating several improvements that allow a better estimation of G_RVS. These improvements pertain to the stray-light background estimation, the line spread function calibration, and the detection of spectra contaminated by nearby relatively bright sources. We calibrated the G_RVS zero-point every 30 hours based on the reference magnitudes of constant stars from the Hipparcos catalogue, and used them to transform the integrated flux of the cleaned and calibrated spectra into epoch magnitudes. The G_RVS magnitude of a star published in DR3 is the median of the epoch magnitudes for that star. We estimated the G_RVS passband by comparing the RVS spectra of 108 bright stars with their flux-calibrated spectra from external spectrophotometric libraries. The G_RVS magnitude provides information that is complementary to that obtained from the G, G_BP, and G_RP magnitudes, which is useful for constraining stellar metallicity and interstellar extinction. The median precision of G_RVS measurements ranges from about 0.006 mag for the brighter stars (i.e. with 3.5 < G_RVS < 6.5 mag) to 0.125 mag at the faint end. The derived G_RVS passband shows that the effective transmittance of the RVS is approximately 1.23 times better than the pre-launch estimate.Comment: 16 pages, 18 figures. Accepted for publication in A&

The French Didactic Tradition in Mathematics

This chapter presents the French didactic tradition. It first describes theemergence and development of this tradition according to four key features (role ofmathematics and mathematicians, role of theories, role of design of teaching andlearning environments, and role of empirical research), and illustrates it through two case studies respectively devoted to research carried out within this traditionon algebra and on line symmetry-reflection. It then questions the influence of thistradition through the contributions of four researchers from Germany, Italy, Mexicoand Tunisia, before ending with a short epilogue