Tests of General relativity with planetary orbits and Monte Carlo simulations

Based on the new developped planetary ephemerides INPOP13c, determinations of acceptable intervals of General Relativity violation in considering simultaneously the PPN parameters $\beta$, PPN $\gamma$, the flattening of the sun $J_{2}^\odot$ and time variation of the gravitational mass of the sun $\mu$ are obtained in using Monte Carlo simulation coupled with basic genetic algorithm. Possible time variations of the gravitational constant G are also deduced. Discussions are lead about the better choice of indicators for the goodness-of-fit for each run and limits consistent with general relativity are obtained simultaneously.Comment: submitte

Lunar laser ranging in infrfared at hte Grasse laser station

For many years, lunar laser ranging (LLR) observations using a green wavelength have suffered an inhomogeneity problem both temporally and spatially. This paper reports on the implementation of a new infrared detection at the Grasse LLR station and describes how infrared telemetry improves this situation. Our first results show that infrared detection permits us to densify the observations and allows measurements during the new and the full Moon periods. The link budget improvement leads to homogeneous telemetric measurements on each lunar retro-reflector. Finally, a surprising result is obtained on the Lunokhod 2 array which attains the same efficiency as Lunokhod 1 with an infrared laser link, although those two targets exhibit a differential efficiency of six with a green laser link

Elucidating molecular connetion between IAHSP onset and Alsin protein by means of Homology Modelling and Molecular Dynamics

The Infantile-onset Ascending Hereditary Spastic Paralysis (IAHSP) is an incurable rare neurodegerative disease related to a mutation-driven aberrant behaviour of the Alsin protein. The lack of information on Alsin atomic structure limits a complete understanding on pathology mechanisms. In this work, molecular modelling techniques have been applied to shed lights on Alsin folding dynamics and misfunction induced by aberrant mutations

Innovative approach for a classic target: fragment screening on trypanothione reductase reveals new opportunities for drug design

Trypanothione reductase (TR) is a key factor in the redox homeostasis of trypanosomatid parasites, critical for survival in the hostile oxidative environment generated by the host to fight infection. TR is considered an attractive target for the development of new trypanocidal agents as it is essential for parasite survival but has no close homolog in humans. However, the high efficiency and turnover of TR challenging targets since only potent inhibitors, with nanomolar IC50, can significantly affect parasite redox state and viability. To aid the design of effective compounds targeting TR, we performed a fragment-based crystal screening at the Diamond Light Source XChem facility using a library optimized for follow-up synthesis steps. The experiment, allowing for testing over 300 compounds, resulted in the identification of 12 new ligands binding five different sites. Interestingly, the screening revealed the existence of an allosteric pocket close to the NADPH binding site, named the "doorstop pocket" since ligands binding at this site interfere with TR activity by hampering the "opening movement" needed to allow cofactor binding. The second remarkable site, known as the Z-site, identified by the screening, is located within the large trypanothione cavity but corresponds to a region not yet exploited for inhibition. The fragments binding to this site are close to each other and have some remarkable features making them ideal for follow-up optimization as a piperazine moiety in three out of five fragments

ALS2-Related Motor Neuron Diseases: From Symptoms to Molecules

Infantile-onset Ascending Hereditary Spastic Paralysis, Juvenile Primary Lateral Sclerosis and Juvenile Amyotrophic Lateral Sclerosis are all motor neuron diseases related to mutations on the ALS2 gene, encoding for a 1657 amino acids protein named Alsin. This ~185 kDa multi-domain protein is ubiquitously expressed in various human tissues, mostly in the brain and the spinal cord. Several investigations have indicated how mutations within Alsin’s structured domains may be responsible for the alteration of Alsin’s native oligomerization state or Alsin’s propensity to interact with protein partners. In this review paper, we propose a description of differences and similarities characterizing the above-mentioned ALS2-related rare neurodegenerative disorders, pointing attention to the effects of ALS2 mutation from molecule to organ and at the system level. Known cases were collected through a literature review and rationalized to deeply elucidate the neurodegenerative clinical outcomes as consequences of ALS2 mutation

Time Biases in Laser Ranging Measurements: Impacts on Geodetic Products Reference Frame and Orbitography

No abstract availabl

Structural insights into the DNA recognition mechanism by the bacterial transcription factor PdxR

This is the final version. Available from Oxford University Press via the DOI in this record.Atomic coordinates and structure factors for the reported apo-PdxR crystal structure have been deposited with the RCSB Protein Data Bank (PDB) under accession number 7PQ9. The cryo-EM maps of the holo-PdxR–DNA complex in the open, half-closed, and closed (C1 and C2 symmetry) conformation and the relative coordinates generated and analysed in the current study have been deposited in the Electron Microscopy Data Bank (EMDB) and in the PDB under accession code EMD-14960 (PDB 7ZTH), EMD-14778 (PDB 7ZLA), EMD-14852 (PDB 7ZPA) and EMD-14801 (PDB 7ZN5), respectively.Specificity in protein-DNA recognition arises from the synergy of several factors that stem from the structural and chemical signatures encoded within the targeted DNA molecule. Here, we deciphered the nature of the interactions driving DNA recognition and binding by the bacterial transcription factor PdxR, a member of the MocR family responsible for the regulation of pyridoxal 5'-phosphate (PLP) biosynthesis. Single particle cryo-EM performed on the PLP-PdxR bound to its target DNA enabled the isolation of three conformers of the complex, which may be considered as snapshots of the binding process. Moreover, the resolution of an apo-PdxR crystallographic structure provided a detailed description of the transition of the effector domain to the holo-PdxR form triggered by the binding of the PLP effector molecule. Binding analyses of mutated DNA sequences using both wild type and PdxR variants revealed a central role of electrostatic interactions and of the intrinsic asymmetric bending of the DNA in allosterically guiding the holo-PdxR-DNA recognition process, from the first encounter through the fully bound state. Our results detail the structure and dynamics of the PdxR-DNA complex, clarifying the mechanism governing the DNA-binding mode of the holo-PdxR and the regulation features of the MocR family of transcription factors.Italian MIUR-PRIN 2020POR FESR Lazio 2014–2020Sapienza University of RomeDefence Science and Technology Laboratory (DSTL)Istituto Pasteur Italia – Fondazione Cenci Bolognett

Altimetry for the future: Building on 25 years of progress

In 2018 we celebrated 25 years of development of radar altimetry, and the progress achieved by this methodology in the fields of global and coastal oceanography, hydrology, geodesy and cryospheric sciences. Many symbolic major events have celebrated these developments, e.g., in Venice, Italy, the 15th (2006) and 20th (2012) years of progress and more recently, in 2018, in Ponta Delgada, Portugal, 25 Years of Progress in Radar Altimetry. On this latter occasion it was decided to collect contributions of scientists, engineers and managers involved in the worldwide altimetry community to depict the state of altimetry and propose recommendations for the altimetry of the future. This paper summarizes contributions and recommendations that were collected and provides guidance for future mission design, research activities, and sustainable operational radar altimetry data exploitation. Recommendations provided are fundamental for optimizing further scientific and operational advances of oceanographic observations by altimetry, including requirements for spatial and temporal resolution of altimetric measurements, their accuracy and continuity. There are also new challenges and new openings mentioned in the paper that are particularly crucial for observations at higher latitudes, for coastal oceanography, for cryospheric studies and for hydrology. The paper starts with a general introduction followed by a section on Earth System Science including Ocean Dynamics, Sea Level, the Coastal Ocean, Hydrology, the Cryosphere and Polar Oceans and the ‘‘Green” Ocean, extending the frontier from biogeochemistry to marine ecology. Applications are described in a subsequent section, which covers Operational Oceanography, Weather, Hurricane Wave and Wind Forecasting, Climate projection. Instruments’ development and satellite missions’ evolutions are described in a fourth section. A fifth section covers the key observations that altimeters provide and their potential complements, from other Earth observation measurements to in situ data. Section 6 identifies the data and methods and provides some accuracy and resolution requirements for the wet tropospheric correction, the orbit and other geodetic requirements, the Mean Sea Surface, Geoid and Mean Dynamic Topography, Calibration and Validation, data accuracy, data access and handling (including the DUACS system). Section 7 brings a transversal view on scales, integration, artificial intelligence, and capacity building (education and training). Section 8 reviews the programmatic issues followed by a conclusion