Visualizing Compaction of Polysomes in Bacteria.

International audienceDuring protein synthesis, many translating ribosomes are bound together with an mRNA molecule to form polysomes (or polyribosomes). While the spatial organization of bacterial polysomes has been well studied in vitro, little is known about how they cluster when cellular conditions are highly constrained. To better understand this, we used electron tomography, template matching, and three-dimensional modeling to analyze the supramolecular network of ribosomes after induction of translational pauses. In Escherichia coli, we overexpressed an mRNA carrying a polyproline motif known to induce pausing during translation. When working with a strain lacking transfer-messenger RNA, the principle actor in the "trans-translation" rescuing system, the cells survived the hijacking of the translation machinery but this resulted in a sharp modification of the ribosomal network. The results of our experiments demonstrate that single ribosomes are replaced with large amounts of compacted polysomes. These polysomes are highly organized, principally forming hairpins and dimers of hairpins that stack together. We propose that these spatial arrangements help maintain translation efficiency when the rescue systems are absent or overwhelmed

Nano-ridge engineering of GaSb for the integration of InAs/GaSb heterostructures on 300 mm (001) Si

Nano-ridge engineering (NRE) is a novel heteroepitaxial approach for the monolithic integration of lattice-mismatched III-V devices on Si substrates. It has been successfully applied to GaAs for the realization of nano-ridge (NR) laser diodes and heterojunction bipolar transistors on 300 mm Si wafers. In this report we extend NRE to GaSb for the integration of narrow bandgap heterostructures on Si. GaSb is deposited by selective area growth in narrow oxide trenches fabricated on 300 mm Si substrates to reduce the defect density by aspect ratio trapping. The GaSb growth is continued and the NR shape on top of the oxide pattern is manipulated via NRE to achieve a broad (001) NR surface. The impact of different seed layers (GaAs and InAs) on the threading dislocation and planar defect densities in the GaSb NRs is investigated as a function of trench width by using transmission electron microscopy (TEM) as well as electron channeling contrast imaging (ECCI), which provides significantly better defect statistics in comparison to TEM only. An InAs/GaSb multi-layer heterostructure is added on top of an optimized NR structure. The high crystal quality and low defect density emphasize the potential of this monolithic integration approach for infrared optoelectronic devices on 300 mm Si substrates

Reflux of Endoplasmic Reticulum proteins to the cytosol inactivates tumor suppressors

International audienceIn the past decades, many studies reported the presence of endoplasmic reticulum (ER)-resident proteins in the cytosol. However, the mechanisms by which these proteins relocate and whether they exert cytosolic functions remain unknown. We find that a subset of ER luminal proteins accumulates in the cytosol of glioblastoma cells isolated from mouse and human tumors. In cultured cells, ER protein reflux to the cytosol occurs upon ER proteostasis perturbation. Using the ER luminal protein anterior gradient 2 (AGR2) as a proof of concept, we tested whether the refluxed proteins gain new functions in the cytosol. We find that refluxed, cytosolic AGR2 binds and inhibits the tumor suppressor p53. These data suggest that ER reflux constitutes an ER surveillance mechanism to relieve the ER from its contents upon stress, providing a selective advantage to tumor cells through gain-of-cytosolic functions-a phenomenon we name ER to Cytosol Signaling (ERCYS)

Fabrication of LTCC Micro-fluidic Devices Using Sacrificial Carbon Layers

Ease of fabrication and design flexibility are two attractive features of low temperature co-fired ceramics (LTCC) technology for fabrication of complex micro-fluidic devices. Such structures are designed and processed using different shaping methods, the extent and complexity of which depends on the final device specifications (dimensions, mechanical and functional properties). In this work, we propose a sacrificial layer method based on carbon-black paste, which burns out during the LTCC firing stage. The paper will summarize the preparation of the paste, influence of processing conditions on the final dimensions, and demonstrate the mechanically integrated structures obtained using this technique. Some of those are membranes of various diameters (7-12mm) with a thickness of 40µm and a variety of internal spacing (15-60µm), free-hanging thick-film resistors (TFR) bridges on LTCC for heating micro-volumes. The main methods of the study will be thermo gravimetric analysis (TGA), scanning electron microscopy (SEM) and dilatometry in addition to electronic instruments for device characterization

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

Fundam Clin Pharmacol

BACKGROUND: Due to its psychoactive effects, ketamine has become a drug used for non-medical purpose. OBJECTIVES: To assess the latest trends in ketamine use among people with substance use disorder and to characterize its clinical complications using complementary health data sources of the French Addictovigilance Network. METHODS: First, we extracted all reports involving ketamine from 2012 to 2021 from the database of the OPPIDUM program (i.e., a multicentric program conducted in collaboration with hundreds of substance abuse treatment facilities that collects data on drugs used by subjects with substance use disorders). We described the reports globally and the changes from 2012 to 2021. Second, we extracted all cases involving ketamine from July 2020 to December 2022 from the French National Pharmacovigilance Database (BNPV). We identified the cases related to ketamine use among people with substance use disorder and described them. RESULTS: There was a 2.5-fold increase in the number of ketamine users with substance use disorder in the OPPIDUM program, from 35 (0.7%) subjects in 2012 to 89 (1.7%) subjects in 2021. There was an increase in the proportion of subjects who were daily users, had distress upon discontinuation, and presented addiction. There were 238 cases related to ketamine use among people with substance use disorder in the French National Pharmacovigilance Database from July 2020 to December 2022. Among them, 94 (39.5%) cases involved ketamine use disorder, 20 (8.4%) cases involved urinary tract and kidney symptoms, and 13 (5.5%) cases involved hepatobiliary symptoms. CONCLUSION: The trend observed over 10 years reflects the growth in ketamine use among people with substance use disorder, although it does not allow to estimate the rates of non-medical use of ketamine in the general population. Ketamine-induced uropathy and cholangiopathy are reported in ketamine users with substance use disorder, especially in case of repeated and/or prolonged use of high doses

Permafrost is warming at a global scale

Permafrost warming has the potential to amplify global climate change, because when frozen sediments thaw it unlocks soil organic carbon. Yet to date, no globally consistent assessment of permafrost temperature change has been compiled. Here we use a global data set of permafrost temperature time series from the Global Terrestrial Network for Permafrost to evaluate temperature change across permafrost regions for the period since the International Polar Year (2007-2009). During the reference decade between 2007 and 2016, ground temperature near the depth of zero annual amplitude in the continuous permafrost zone increased by 0.39 ± 0.15 °C. Over the same period, discontinuous permafrost warmed by 0.20 ± 0.10 °C. Permafrost in mountains warmed by 0.19 ± 0.05 °C and in Antarctica by 0.37 ± 0.10 °C. Globally, permafrost temperature increased by 0.29 ± 0.12 °C. The observed trend follows the Arctic amplification of air temperature increase in the Northern Hemisphere. In the discontinuous zone, however, ground warming occurred due to increased snow thickness while air temperature remained statistically unchanged

How collective is collective efficacy? The importance of consensus in judgments about community cohesion and willingness to intervene

Existing studies have generally measured collective efficacy by combining survey respondents’ ratings of their local area into an overall summary for each neighborhood. Naturally, this approach results in a substantive focus on the variation in average levels of collective efficacy between neighborhoods. In this article, we focus on the variation in consensus of collective efficacy judgments. To account for differential consensus among neighborhoods, we use a mixed‐effects location‐scale model, with variability in the consensus of judgments treated as an additional neighborhood‐level random effect. Our results show that neighborhoods in London differ, not just in their average levels of collective efficacy but also in the extent to which residents agree with one another in their assessments. In accord with findings for U.S. cities, our results show that consensus in collective efficacy assessments is affected by the ethnic composition of neighborhoods. Additionally, we show that heterogeneity in collective efficacy assessments is consequential, with higher levels of criminal victimization, worry about crime, and risk avoidance behavior in areas where collective efficacy consensus is low