Dynamic changes in eIF4F-mRNA interactions revealed by global analyses of environmental stress responses

BACKGROUND: Translation factors eIF4E and eIF4G form eIF4F, which interacts with the messenger RNA (mRNA) 5' cap to promote ribosome recruitment and translation initiation. Variations in the association of eIF4F with individual mRNAs likely contribute to differences in translation initiation frequencies between mRNAs. As translation initiation is globally reprogrammed by environmental stresses, we were interested in determining whether eIF4F interactions with individual mRNAs are reprogrammed and how this may contribute to global environmental stress responses. RESULTS: Using a tagged-factor protein capture and RNA-sequencing (RNA-seq) approach, we have assessed how mRNA associations with eIF4E, eIF4G1 and eIF4G2 change globally in response to three defined stresses that each cause a rapid attenuation of protein synthesis: oxidative stress induced by hydrogen peroxide and nutrient stresses caused by amino acid or glucose withdrawal. We find that acute stress leads to dynamic and unexpected changes in eIF4F-mRNA interactions that are shared among each factor and across the stresses imposed. eIF4F-mRNA interactions stabilised by stress are predominantly associated with translational repression, while more actively initiating mRNAs become relatively depleted for eIF4F. Simultaneously, other mRNAs are insulated from these stress-induced changes in eIF4F association. CONCLUSION: Dynamic eIF4F-mRNA interaction changes are part of a coordinated early translational control response shared across environmental stresses. Our data are compatible with a model where multiple mRNA closed-loop complexes form with differing stability. Hence, unexpectedly, in the absence of other stabilising factors, rapid translation initiation on mRNAs correlates with less stable eIF4F interactions

Re-Patterning Sleep Architecture in Drosophila through Gustatory Perception and Nutritional Quality

Organisms perceive changes in their dietary environment and enact a suite of behavioral and metabolic adaptations that can impact motivational behavior, disease resistance, and longevity. However, the precise nature and mechanism of these dietary responses is not known. We have uncovered a novel link between dietary factors and sleep behavior in Drosophila melanogaster. Dietary sugar rapidly altered sleep behavior by modulating the number of sleep episodes during both the light and dark phase of the circadian period, independent of an intact circadian rhythm and without affecting total sleep, latency to sleep, or waking activity. The effect of sugar on sleep episode number was consistent with a change in arousal threshold for waking. Dietary protein had no significant effect on sleep or wakefulness. Gustatory perception of sugar was necessary and sufficient to increase the number of sleep episodes, and this effect was blocked by activation of bitter-sensing neurons. Further addition of sugar to the diet blocked the effects of sweet gustatory perception through a gustatory-independent mechanism. However, gustatory perception was not required for diet-induced fat accumulation, indicating that sleep and energy storage are mechanistically separable. We propose a two-component model where gustatory and metabolic cues interact to regulate sleep architecture in response to the quantity of sugar available from dietary sources. Reduced arousal threshold in response to low dietary availability may have evolved to provide increased responsiveness to cues associated with alternative nutrient-dense feeding sites. These results provide evidence that gustatory perception can alter arousal thresholds for sleep behavior in response to dietary cues and provide a mechanism by which organisms tune their behavior and physiology to environmental cues

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

V/MCM-41 as catalyst for asymmetric and non-asymmetric oxidation of methyl phenyl sulfide

V/MCM-41 was prepared by impregnation of MCM-41, calcined at two different temperatures (550 and 750 °C), with vanadium (V) oxytriisopropoxide (VO(OiPr)3). The calcination temperature of the support controls the surface silanol density, leading to different surface organometallic species, as shown by different characterisation techniques, such as 29Si CP-MAS NMR, UV-Vis and FT-IR. Monopodal ≡SiO-VO(O iPr)2 and bipodal (≡SiO)2-VO(O iPr) species are the major ones in V-MCM750, whereas bipodal and tripodal (≡SiO)3-VO are the major ones in V-MCM550. Monopodal and bipodal species are more active in the oxidation of methyl phenyl sulfide with alkyl hydroperoxides, with higher selectivity to sulfoxide than tripodal ones, but at the same time they are more easily deactivated. It is possible to perform the enantioselective oxidation using (S,S)-(+)-N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2- cyclohexanediamine as chiral ligand, with the monopodal species being the most efficient.Peer Reviewe

Vanadium-Schiff base complex covalently bonded on modified MCM-41 as catalyst for asymmetric oxidation of methyl phenyl sulfide

The vanadium-Schiff base complex was immobilized on mesoporous MCM-41 by a covalent grafting method using 3-aminopropyltriethoxysilane as a reactive surface modifier. The formation and integrity of the complex have been studied using XRD, FT-IR, UV–Vis, ESR, Si-MAS-NMR and N adsorption–desorption. The heterogeneous VO(Schiff)-MCM catalyst shows an activity and an enantioselectivity comparable to those obtained with the homogeneous catalyst VO(Schiff), for the asymmetric oxidation of methyl phenyl sulfide. The combination of the heterogenous catalyst with CHP as oxidant offers a selective catalytic system for oxidation of methyl phenyl sulfide with a significant enantioselectivity in the range of 17–23 % ee. In addition, the heterogeneized catalyst could be easily separated from the products and reused.Peer Reviewe

New bis(oxazoline)–vanadyl complexes, supported by electrostatic interaction in Laponite clay, as heterogeneous catalysts for asymmetric oxidation of methyl phenyl sulfide

Chiral bis(oxazoline) ligands are used for the first time to promote the enantioselective vanadium-catalyzed oxidation of sulfides with alkyl hydroperoxides. Several bis(oxazoline)-VO complexes have been prepared and supported by cation exchange in Laponite clay. The substituent in the oxazoline ring, and the type of hydroperoxide are relevant parameters that control the activity and selectivity of the resulting catalysts. Tert-butyl hydroperoxide is more reactive but less enantioselective than cumenehydroperoxide, both with the neat and supported VO-bis(oxazoline) complexes. Activities and enantioselectivities obtained with the heterogeneous catalysts are always lower than in solution, and in general better and more consistent results are obtained with box(Pr) ligand which seems to be also the best chiral auxiliary in homogeneous phase, leading to a modest but significant enantioselectivity of 20% ee in heterogeneous phase and of 28% in homogeneous phase. The recovered of the best catalyst shows a decrease in the catalytic activity and in the enantioselectivity, in agreement with some decomplexation of the chiral ligand, whereas the supported vanadium species remain stable and recoverable.Financial support from the Spanish Ministerio de Economía y Competitividad (Project CTQ2014-52367-R) and the Diputación General de Aragón (E11 Group co-financed by the European Regional Development Funds) is gratefully acknowledged. M. F. thanks theTunisien Ministère de l’Enseignement Supérieure et la Recherche Scientifique for a short-mobility grant (bourse d'alternance).Peer Reviewe

Intérêt du Télos dans l'évaluation de la laxité chronique antérieure du genou en pré- et en postopératoire

Le Télos est une technique de radiographie dynamique, mécanique, passive, comparative et reproductible, fixant sur un cliché le test de Lachman (cliché de Lachman passif). La laximétrie au Télos s'avère un complément objectif à l'examen clinique pour atteindre un triple but : diagnostique, pronostique et thérapeutiqu

Setting the Scene

International audienc