30 research outputs found
An overview of siderophore biosynthesis among fluorescent Pseudomonads and new insights into their complex cellular organization
Exploring protein–protein interactions with large differences in protein expression levels using FLIM-FRET
FRET-FLIM and single molecule tracking reveal the supra-molecular organization of the pyoverdine bio-synthetic enzymes in Pseudomonas aeruginosa.
Glissile dislocations with transient cores in silicon
We report an unexpected characteristic of dislocation cores in silicon. Using
first-principles calculations, we show that all the stable core configurations
for a non-dissociated 60 dislocation are sessile. The only glissile
configuration, previously obtained by nucleation from surfaces, surprinsingly
corresponds to an unstable core. As a result, the 60 dislocation motion
is solely driven by stress, with no thermal activation. We predict that this
original feature could be relevant in situations for which large stresses
occur, such as mechanical deformation at room temperature. Our work also
suggests that post-mortem observations of stable dislocations could be
misleading, and that mobile unstable dislocation cores should be taken into
account in theoretical investigations
Nucleic Acids Res
The HIV-1 nucleocapsid protein (NCp7) is a nucleic acid chaperone required during reverse transcription. During the first strand transfer, NCp7 is thought to destabilize cTAR, the (-)DNA copy of the TAR RNA hairpin, and subsequently direct the TAR/cTAR annealing through the zipping of their destabilized stem ends. To further characterize the destabilizing activity of NCp7, we locally probe the structure and dynamics of cTAR by steady-state and time resolved fluorescence spectroscopy. NC(11-55), a truncated NCp7 version corresponding to its zinc-finger domain, was found to bind all over the sequence and to preferentially destabilize the penultimate double-stranded segment in the lower part of the cTAR stem. This destabilization is achieved through zinc-finger-dependent binding of NC to the G(10) and G(50) residues. Sequence comparison further revealed that C*A mismatches close to the two G residues were critical for fine tuning the stability of the lower part of the cTAR stem and conferring to G(10) and G(50) the appropriate mobility and accessibility for specific recognition by NC. Our data also highlight the necessary plasticity of NCp7 to adapt to the sequence and structure variability of cTAR to chaperone its annealing with TAR through a specific pathway
Nucleic Acids Res
The HIV-1 transactivator of transcription (Tat) protein is thought to stimulate reverse transcription (RTion). The Tat protein and, more specifically, its (44-61) domain were recently shown to promote the annealing of complementary DNA sequences representing the HIV-1 transactivation response element TAR, named dTAR and cTAR, that plays a key role in RTion. Moreover, the kinetic mechanism of the basic Tat(44-61) peptide in this annealing further revealed that this peptide constitutes a representative nucleic acid annealer. To further understand the structure-activity relationships of this highly conserved domain, we investigated by electrophoresis and fluorescence approaches the binding and annealing properties of various Tat(44-61) mutants. Our data showed that the Tyr47 and basic residues of the Tat(44-61) domain were instrumental for binding to cTAR through stacking and electrostatic interactions, respectively, and promoting its annealing with dTAR. Furthermore, the annealing efficiency of the mutants clearly correlates with their ability to rapidly associate and dissociate the complementary oligonucleotides and to promote RTion. Thus, transient and dynamic nucleic acid interactions likely constitute a key mechanistic component of annealers and the role of Tat in the late steps of RTion. Finally, our data suggest that Lys50 and Lys51 acetylation regulates Tat activity in RTion
Evaluating the spatial uncertainty of future land abandonment in a mountain valley (Vicdessos, Pyrenees-France) : insights form model parameterization and experiments
International audienceEuropean mountains are particularly sensitive to climatic disruptions and land use changes. The latter leads to high rates of natural reforestation over the last 50 years. Faced with the challenge of predicting possible impacts on ecosystem services, LUCC models offer new opportunities for land managers to adapt or mitigate their strategies. Assessing the spatial uncertainty of future LUCC is crucial for the defintion of sustainable land use strategies. However, the sources of uncertainty may differ, including the input parameters, the model itself, and the wide range of possible futures. The aim of this paper is to propose a method to assess the probability of occurrence of future LUCC that combines the inherent uncertainty of model parameterization and the ensemble uncertainty of the future based scenarios. For this purpose, we used the Land Change Modeler tool to simulate future LUCC on a study site located in the Pyrenees Mountains (France) and 2 scenarios illustratins 2 land use strategies. The model was parameterized with the same driving factors used for its calibration. The defintion of static vs. dynamic and quantitative vs. qualitative (discretized) driving factors, and their combination resulted in 4 parameterizations. The combination of model outcomes produced maps of spatial uncertainty of future LUCC. This work involves literature to future-based LUCC studies. It goes beyond the uncertainty of simulation models by integrating the unceertainty of the future to provide maps to help decision makers and land managers
CTL Escape Mediated by Proteasomal Destruction of an HIV-1 Cryptic Epitope
Cytotoxic CD8+ T cells (CTLs) play a critical role in controlling viral
infections. HIV-infected individuals develop CTL responses against epitopes
derived from viral proteins, but also against cryptic epitopes encoded by viral
alternative reading frames (ARF). We studied here the mechanisms of HIV-1 escape
from CTLs targeting one such cryptic epitope, Q9VF, encoded by an
HIVgag ARF and presented by HLA-B*07. Using PBMCs of
HIV-infected patients, we first cloned and sequenced proviral DNA encoding for
Q9VF. We identified several polymorphisms with a minority of proviruses encoding
at position 5 an aspartic acid (Q9VF/5D) and a majority encoding an asparagine
(Q9VF/5N). We compared the prevalence of each variant in PBMCs of
HLA-B*07+ and HLA-B*07- patients. Proviruses encoding Q9VF/5D were
significantly less represented in HLA-B*07+ than in HLA-B*07-
patients, suggesting that Q9FV/5D encoding viruses might be under selective
pressure in HLA-B*07+ individuals. We thus analyzed ex
vivo CTL responses directed against Q9VF/5D and Q9VF/5N. Around
16% of HLA-B*07+ patients exhibited CTL responses targeting Q9VF
epitopes. The frequency and the magnitude of CTL responses induced with Q9VF/5D
or Q9VF/5N peptides were almost equal indicating a possible cross-reactivity of
the same CTLs on the two peptides. We then dissected the cellular mechanisms
involved in the presentation of Q9VF variants. As expected, cells infected with
HIV strains encoding for Q9VF/5D were recognized by Q9VF/5D-specific CTLs. In
contrast, Q9VF/5N-encoding strains were neither recognized by Q9VF/5N- nor by
Q9VF/5D-specific CTLs. Using in vitro proteasomal digestions
and MS/MS analysis, we demonstrate that the 5N variation introduces a strong
proteasomal cleavage site within the epitope, leading to a dramatic reduction of
Q9VF epitope production. Our results strongly suggest that HIV-1 escapes CTL
surveillance by introducing mutations leading to HIV ARF-epitope destruction by
proteasomes
The Athena X-ray Integral Field Unit: a consolidated design for the system requirement review of the preliminary definition phase
The Athena X-ray Integral Unit (X-IFU) is the high resolution X-ray
spectrometer, studied since 2015 for flying in the mid-30s on the Athena space
X-ray Observatory, a versatile observatory designed to address the Hot and
Energetic Universe science theme, selected in November 2013 by the Survey
Science Committee. Based on a large format array of Transition Edge Sensors
(TES), it aims to provide spatially resolved X-ray spectroscopy, with a
spectral resolution of 2.5 eV (up to 7 keV) over an hexagonal field of view of
5 arc minutes (equivalent diameter). The X-IFU entered its System Requirement
Review (SRR) in June 2022, at about the same time when ESA called for an
overall X-IFU redesign (including the X-IFU cryostat and the cooling chain),
due to an unanticipated cost overrun of Athena. In this paper, after
illustrating the breakthrough capabilities of the X-IFU, we describe the
instrument as presented at its SRR, browsing through all the subsystems and
associated requirements. We then show the instrument budgets, with a particular
emphasis on the anticipated budgets of some of its key performance parameters.
Finally we briefly discuss on the ongoing key technology demonstration
activities, the calibration and the activities foreseen in the X-IFU Instrument
Science Center, and touch on communication and outreach activities, the
consortium organisation, and finally on the life cycle assessment of X-IFU
aiming at minimising the environmental footprint, associated with the
development of the instrument. Thanks to the studies conducted so far on X-IFU,
it is expected that along the design-to-cost exercise requested by ESA, the
X-IFU will maintain flagship capabilities in spatially resolved high resolution
X-ray spectroscopy, enabling most of the original X-IFU related scientific
objectives of the Athena mission to be retained. (abridged).Comment: 48 pages, 29 figures, Accepted for publication in Experimental
Astronomy with minor editin
The Athena X-ray Integral Field Unit: a consolidated design for the system requirement review of the preliminary definition phase
The Athena X-ray Integral Unit (X-IFU) is the high resolution X-ray spectrometer studied since 2015 for flying in the mid-30s on the Athena space X-ray Observatory. Athena is a versatile observatory designed to address the Hot and Energetic Universe science theme, as selected in November 2013 by the Survey Science Committee. Based on a large format array of Transition Edge Sensors (TES), X-IFU aims to provide spatially resolved X-ray spectroscopy, with a spectral resolution of 2.5 eV (up to 7 keV) over a hexagonal field of view of 5 arc minutes (equivalent diameter). The X-IFU entered its System Requirement Review (SRR) in June 2022, at about the same time when ESA called for an overall X-IFU redesign (including the X-IFU cryostat and the cooling chain), due to an unanticipated cost overrun of Athena. In this paper, after illustrating the breakthrough capabilities of the X-IFU, we describe the instrument as presented at its SRR (i.e. in the course of its preliminary definition phase, so-called B1), browsing through all the subsystems and associated requirements. We then show the instrument budgets, with a particular emphasis on the anticipated budgets of some of its key performance parameters, such as the instrument efficiency, spectral resolution, energy scale knowledge, count rate capability, non X-ray background and target of opportunity efficiency. Finally, we briefly discuss the ongoing key technology demonstration activities, the calibration and the activities foreseen in the X-IFU Instrument Science Center, touch on communication and outreach activities, the consortium organisation and the life cycle assessment of X-IFU aiming at minimising the environmental footprint, associated with the development of the instrument. Thanks to the studies conducted so far on X-IFU, it is expected that along the design-to-cost exercise requested by ESA, the X-IFU will maintain flagship capabilities in spatially resolved high resolution X-ray spectroscopy, enabling most of the original X-IFU related scientific objectives of the Athena mission to be retained. The X-IFU will be provided by an international consortium led by France, The Netherlands and Italy, with ESA member state contributions from Belgium, Czech Republic, Finland, Germany, Poland, Spain, Switzerland, with additional contributions from the United States and Japan.The French contribution to X-IFU is funded by CNES, CNRS and CEA. This work has been also supported by ASI (Italian Space Agency) through the Contract 2019-27-HH.0, and by the ESA (European Space Agency) Core Technology Program (CTP) Contract No. 4000114932/15/NL/BW and the AREMBES - ESA CTP No.4000116655/16/NL/BW. This publication is part of grant RTI2018-096686-B-C21 funded by MCIN/AEI/10.13039/501100011033 and by “ERDF A way of making Europe”. This publication is part of grant RTI2018-096686-B-C21 and PID2020-115325GB-C31 funded by MCIN/AEI/10.13039/501100011033