Covid-19 Impact on higher education. Comparative analysis of the Europaeum member universities. Report 2020.

Fac. de Ciencias de la InformaciónFALSEpu

Cerebral organoids derived from Sandhoff disease-induced pluripotent stem cells exhibit impaired neurodifferentiation

Sandhoff disease, one of the GM2 gangliosidoses, is a lysosomal storage disorder characterized by the absence of beta-hexosaminidase A and B activity and the concomitant lysosomal accumulation of its substrate, GM2 ganglioside. It features catastrophic neurodegeneration and death in early childhood. How the lysosomal accumulation of ganglioside might affect the early development of the nervous system is not understood. Recently, cerebral organoids derived from induced pluripotent stem (iPS) cells have illuminated early developmental events altered by disease processes. To develop an early neurodevelopmental model of Sandhoff disease, we first generated iPS cells from the fibroblasts of an infantile Sandhoff disease patient, then corrected one of the mutant HEXB alleles in those iPS cells using CRISPR/Cas9 genome-editing technology, thereby creating isogenic controls. Next, we used the parental Sandhoff disease iPS cells and isogenic HEXB-corrected iPS cell clones to generate cerebral organoids that modeled the first trimester of neurodevelopment. The Sandhoff disease organoids, but not the HEXB-corrected organoids, accumulated GM2 ganglioside and exhibited increased size and cellular proliferation compared with the HEXB-corrected organoids. Whole-transcriptome analysis demonstrated that development was impaired in the Sandhoff disease organoids, suggesting that alterations in neuronal differentiation may occur during early development in the GM2 gangliosidoses

Global Reprogramming of Host SUMOylation during Influenza Virus Infection

Dynamic nuclear SUMO modifications play essential roles in orchestrating cellular responses to proteotoxic stress, DNA damage, and DNA virus infection. Here,we describe a non-canonical host SUMOylation response to the nuclear-replicating RNA pathogen, influenza virus, and identify viral RNA polymerase activity as a major contributor to SUMO proteome re-modeling. Using quantitative proteomics to compare stress-induced SUMOylation responses, we reveal that influenza virus infection triggers unique re-targeting of SUMO to 63 host proteins involved in transcription, mRNA processing, RNA quality control, and DNA damage repair. This is paralleled by widespread host deSUMOylation. Depletion screening identified ten virus-induced SUMO targets as potential antiviral factors, including C18orf25 and the SMC5/6 and PAF1 complexes. Mechanistic studies further uncovered a role for SUMOylation of the PAF1 complex component, parafibromin (CDC73), in potentiating antiviral gene expression. Our global characterization of influenza virus-triggered SUMO redistribution provides a proteomic resource to understand host nuclear SUMOylation responses to infection

Current status of the Spectrograph System for the SuMIRe/PFS

The Prime Focus Spectrograph (PFS) is a new facility instrument for Subaru Telescope which will be installed in around 2017. It is a multi-object spectrograph fed by about 2400 fibers placed at the prime focus covering a hexagonal field-of-view with 1.35 deg diagonals and capable of simultaneously obtaining data of spectra with wavelengths ranging from 0.38 um to 1.26 um. The spectrograph system is composed of four identical modules each receiving the light from 600 fibers. Each module incorporates three channels covering the wavelength ranges 0.38-0.65 mu ("Blue"), 0.63-0.97 mu ("Red"), and 0.94-1.26 mu ("NIR") respectively; with resolving power which progresses fairly smoothly from about 2000 in the blue to about 4000 in the infrared. An additional spectral mode allows reaching a spectral resolution of 5000 at 0.8mu (red). The proposed optical design is based on a Schmidt collimator facing three Schmidt cameras (one per spectral channel). This architecture is very robust, well known and documented. It allows for high image quality with only few simple elements (high throughput) at the expense of the central obscuration, which leads to larger optics. Each module has to be modular in its design to allow for integration and tests and for its safe transport up to the telescope: this is the main driver for the mechanical design. In particular, each module will be firstly fully integrated and validated at LAM (France) before it is shipped to Hawaii. All sub-assemblies will be indexed on the bench to allow for their accurate repositioning. This paper will give an overview of the spectrograph system which has successfully passed the Critical Design Review (CDR) in 2014 March and which is now in the construction phase.Comment: 9 pages, 7 figures, submitted to "Ground-based and Airborne Instrumentation for Astronomy V, Suzanne K. Ramsay, Ian S. McLean, Hideki Takami, Editors, Proc. SPIE 9147 (2014)

SUBARU prime focus spectrograph: integration, testing and performance for the first spectrograph

The Prime Focus Spectrograph (PFS) of the Subaru Measurement of Images and Redshifts (SuMIRe) project for Subaru telescope consists in four identical spectrographs fed by 600 fibers each. Each spectrograph is composed by an optical entrance unit that creates a collimated beam and distributes the light to three channels, two visibles and one near infrared. This paper presents the on-going effort for the tests & integration process for the first spectrograph channel: we have developed a detailed Assembly Integration and Test (AIT) plan, as well as the methods, detailed processes and I&T tools. We describe the tools we designed to assemble the parts and to test the performance of the spectrograph. We also report on the thermal acceptance tests we performed on the first visible camera unit. We also report on and discuss the technical difficulties that did appear during this integration phase. Finally, we detail the important logistic process that is require to transport the components from other country to Marseille

Slx8 removes Pli1-dependent protein-SUMO conjugates including SUMOylated Topoisomerase I to promote genome stability

Peer reviewedPublisher PD

Fast automated placement of polar hydrogen atoms in protein-ligand complexes

<p>Abstract</p> <p>Background</p> <p>Hydrogen bonds play a major role in the stabilization of protein-ligand complexes. The ability of a functional group to form them depends on the position of its hydrogen atoms. An accurate knowledge of the positions of hydrogen atoms in proteins is therefore important to correctly identify hydrogen bonds and their properties. The high mobility of hydrogen atoms introduces several degrees of freedom: Tautomeric states, where a hydrogen atom alters its binding partner, torsional changes where the position of the hydrogen atom is rotated around the last heavy-atom bond in a residue, and protonation states, where the number of hydrogen atoms at a functional group may change. Also, side-chain flips in glutamine and asparagine and histidine residues, which are common crystallographic ambiguities must be identified before structure-based calculations can be conducted.</p> <p>Results</p> <p>We have implemented a method to determine the most probable hydrogen atom positions in a given protein-ligand complex. Optimality of hydrogen bond geometries is determined by an empirical scoring function which is used in molecular docking. This allows to evaluate protein-ligand interactions with an established model. Also, our method allows to resolve common crystallographic ambiguities such as as flipped amide groups and histidine residues. To ensure high speed, we make use of a dynamic programming approach.</p> <p>Conclusion</p> <p>Our results were checked against selected high-resolution structures from an external dataset, for which the positions of the hydrogen atoms have been validated manually. The quality of our results is comparable to that of other programs, with the advantage of being fast enough to be applied on-the-fly for interactive usage or during score evaluation.</p

Prime Focus Spectrograph (PFS) for the Subaru Telescope: Overview, recent progress, and future perspectives

PFS (Prime Focus Spectrograph), a next generation facility instrument on the 8.2-meter Subaru Telescope, is a very wide-field, massively multiplexed, optical and near-infrared spectrograph. Exploiting the Subaru prime focus, 2394 reconfigurable fibers will be distributed over the 1.3 deg field of view. The spectrograph has been designed with 3 arms of blue, red, and near-infrared cameras to simultaneously observe spectra from 380nm to 1260nm in one exposure at a resolution of ~1.6-2.7A. An international collaboration is developing this instrument under the initiative of Kavli IPMU. The project is now going into the construction phase aiming at undertaking system integration in 2017-2018 and subsequently carrying out engineering operations in 2018-2019. This article gives an overview of the instrument, current project status and future paths forward.Comment: 17 pages, 10 figures. Proceeding of SPIE Astronomical Telescopes and Instrumentation 201