Fluorescence and two-photon absorption of push-pull aryl(bi)thiophenes: structure-property relationships

Special Issue in honor of Jean-Pierre SauvagePhotophysical and TPA properties of series of push-pull aryl(bi)thiophene chromophores bearing electron-donating (D) and electron-withdrawing (A) end-groups of increasing strength are presented. All compounds show an intense Intramolecular Charge Transfer (ICT) absorption band in the visible region. Increasing the D and/or A strength as well as the length of the conjugated path induces a bathochromic and hyperchromic of the absorption band as reported for analogous push-pull polyenes. Yet, in contrast with corresponding push-pull polyenes, a significant increase in fluorescence is observed. In particular, chromophores built from a phenyl-bithienyl conjugated path and bearing strong D and A end-groups were found to combine very large one and two-photon brightness as well as strong emission in the red/NIR region. These molecules hold promises as biphotonic fluorescent probes for bioimaging.Fundação para a Ciência e a Tecnologia (FCT

Highly Variable Taxa-specific Coral Bleaching Responses to Thermal Stresses

Complex histories of chronic and acute sea surface temperature (SST) stresses are expected to trigger taxon- and location-specific responses that will ultimately lead to novel coral communities. The 2016 El Niño-Southern Oscillation provided an opportunity to examine large- scale and recent environmental histories on emerging patterns in 226 coral communities distrib- uted across 12 countries from East Africa to Fiji. Six main coral communities were identified that largely varied across a gradient of Acropora to massive Porites dominance. Bleaching intensity was taxon-specific and was associated with complex interactions among the 20 environmental variables that we examined. Coral community structure was better aligned with the historical temperature patterns between 1985 and 2015 than the 2016 extreme temperature event. Addi- tionally, bleaching responses observed during 2016 differed from historical reports during past warm years. Consequently, coral communities present in 2016 are likely to have been reorganized by both long-term community change and acclimation mechanisms. For example, less disturbed sites with cooler baseline temperatures, higher mean historical SST background variability, and infrequent extreme warm temperature stresses were associated with Acropora-dominated communities, while more disturbed sites with lower historical SST background variability and frequent acute warm stress were dominated by stress-resistant massive Porites corals. Overall, the combination of taxon-specific responses, community-level reorganization over time, geographic variation, and multiple environmental stressors suggest complex responses and a diversity of future coral communities that can help contextualize management priorities and activities

Large Geographic Variability in the Resistance of Corals to Thermal Stress

Aim: Predictions for the future of coral reefs are largely based on thermal exposure and poorly account for potential geographic variation in biological sensitivity to ther- mal stress. Without accounting for complex sensitivity responses, simple climate ex- posure models and associated predictions may lead to poor estimates of future coral survival and lead to policies that fail to identify and implement the most appropri- ate interventions. To begin filling this gap, we evaluated a number of attributes of coral taxa and communities that are predicted to influence coral resistance to thermal stress over a large geographic range. Location: Western Indo-Pacific and Central Indo-Pacific Ocean Realms. Major taxa studied: Zooxanthellate Scleractinia – hard corals. Methods: We evaluated the geographic variability of coral resistance to thermal stress as the ratio of thermal exposure and sensitivity in 12 countries during the 2016 global-bleaching event. Thermal exposure was estimated by two metrics: (a) histori- cal excess summer heat (cumulative thermal anomaly, CTA), and (b) a multivariate index of sea-surface temperature (SST), light, and water flow (climate exposure, CE). Sensitivity was estimated for 226 sites using coordinated bleaching observations and underwater surveys of coral communities. We then evaluated coral resistance to ther- mal stress using 48 generalized linear mixed models (GLMMs) to compare the poten- tial influences of geography, historical SST variation, coral cover and coral richness. Results: Geographic faunal provinces and ecoregions were the strongest predic- tors of coral resistance to thermal stress, with sites in the Australian, Indonesian and Fiji-Caroline Islands coral provinces having higher resistance to thermal stress than Africa-India and Japan-Vietnam provinces. Ecoregions also showed strong gradients in resistance with highest resistance to thermal stress in the western Pacific and Coral Triangle and lower resistance in the surrounding ecoregions. A more detailed evaluation of Coral Triangle and non-Coral Triangle sites found higher resistance to thermal stress within the Coral Triangle, associated with c. 2.5 times more recent historical thermal anomalies and more centralized, warmer, and cool-water skew SST distributions, than in non-Coral Triangle sites. Our findings identify the importance of environmental history and geographic context in future predictions of bleaching, and identify some potential drivers of coral resistance to thermal stress. Main conclusions: Simple threshold models of heat stress and coral acclimation are commonly used to predict the future of coral reefs. Here and elsewhere we show that large-scale responses of coral communities to heat stress are geographically variable and associated with differential environmental stresses and histories

Life cycle assessment of Polychlorinated Biphenyl contaminated soil remediation processes

Goal and scope. A life-cycle assessment (LCA) was performed to evaluate the environmental impacts of the remediation of industrial soils contaminated by polychlorobiphenyl (PCB). Two new bioremediation treatment options were compared with the usual incineration process. In this attributional LCA, only secondary impacts were considered. The contaminated soil used for the experiments contained 200 mg of PCB per kg. Methods. Three off-site treatments scenarios were studied: 1) bioremediation with mechanical aeration, 2) bioremediation with electric aeration and 3) incineration with natural gas. Bioremediation processes were designed from lab-scale, scale-up and pilot experiments. The incineration technique was inspired by a French plant. A semi-quantitative uncertainty analysis was performed on the data. Environmental impacts were evaluated with the CML 2001 method using the Simapro software program. Results and discussion. In most compared categories, the bioremediation processes are favorable. Of the bioremediation options, the lowest environmental footprint was observed for electric aeration. The uncertainty analysis supported the results that compared incineration and bioremediation but decreased the difference between the options of aeration. The distance of transportation was one of the most sensitive parameters, especially for bioremediation. At equal distances between the polluted sites and the treatment plant, bioremediation had fewer impacts than incineration in eight out of thirteen categories. Conclusions. The use of natural gas for the incineration process generated the most impacts. Irrespective of the aeration option, bioremediation was better than incineration. Recommendations. The time of treatment should be taken into account. More precise and detailed data are required for the incineration scenario. More parameters of biological treatments should be measured. LCA results should be completed using ecological and health risk assessment and an acceptability evaluation

Correction to: Eight years after an international workshop on myotonic dystrophy patient registries: Case study of a global collaboration for a rare disease (Orphanet Journal of Rare Diseases (2018) 13 (155) DOI: 10.1186/s13023-018-0889-0)

The original version of this article [1] unfortunately included an error to an author\u27s name. Author Jordi Díaz-Manera was erroneously presented as Jorge Alberto Diaz Manera. The correct author name has been included in the author list of this Correction article. For citation purposes the author\u27s given name is Jordi and family name Diaz-Manera. Therefore, the correct citation of the author\u27s details is: Diaz-Manera J

Quantitative and predictive model of kinetic regulation by E. coli TPP riboswitches.

Riboswitches are non-coding elements upstream or downstream of mRNAs that, upon binding of a specific ligand, regulate transcription and/or translation initiation in bacteria, or alternative splicing in plants and fungi. We have studied thiamine pyrophosphate (TPP) riboswitches regulating translation of thiM operon and transcription and translation of thiC operon in E. coli, and that of THIC in the plant A. thaliana. For all, we ascertained an induced-fit mechanism involving initial binding of the TPP followed by a conformational change leading to a higher-affinity complex. The experimental values obtained for all kinetic and thermodynamic parameters of TPP binding imply that the regulation by A. thaliana riboswitch is governed by mass-action law, whereas it is of kinetic nature for the two bacterial riboswitches. Kinetic regulation requires that the RNA polymerase pauses after synthesis of each riboswitch aptamer to leave time for TPP binding, but only when its concentration is sufficient. A quantitative model of regulation highlighted how the pausing time has to be linked to the kinetic rates of initial TPP binding to obtain an ON/OFF switch in the correct concentration range of TPP. We verified the existence of these pauses and the model prediction on their duration. Our analysis also led to quantitative estimates of the respective efficiency of kinetic and thermodynamic regulations, which shows that kinetically regulated riboswitches react more sharply to concentration variation of their ligand than thermodynamically regulated riboswitches. This rationalizes the interest of kinetic regulation and confirms empirical observations that were obtained by numerical simulations

Viral Vector Malaria Vaccines Induce High-Level T Cell and Antibody Responses in West African Children and Infants.

Heterologous prime-boosting with viral vectors encoding the pre-erythrocytic antigen thrombospondin-related adhesion protein fused to a multiple epitope string (ME-TRAP) induces CD8+ T cell-mediated immunity to malaria sporozoite challenge in European malaria-naive and Kenyan semi-immune adults. This approach has yet to be evaluated in children and infants. We assessed this vaccine strategy among 138 Gambian and Burkinabe children in four cohorts: 2- to 6-year olds in The Gambia, 5- to 17-month-olds in Burkina Faso, and 5- to 12-month-olds and 10-week-olds in The Gambia. We assessed induction of cellular immunity, taking into account the distinctive hematological status of young infants, and characterized the antibody response to vaccination. T cell responses peaked 7 days after boosting with modified vaccinia virus Ankara (MVA), with highest responses in infants aged 10 weeks at priming. Incorporating lymphocyte count into the calculation of T cell responses facilitated a more physiologically relevant comparison of cellular immunity across different age groups. Both CD8+ and CD4+ T cells secreted cytokines. Induced antibodies were up to 20-fold higher in all groups compared with Gambian and United Kingdom (UK) adults, with comparable or higher avidity. This immunization regimen elicited strong immune responses, particularly in young infants, supporting future evaluation of efficacy in this key target age group for a malaria vaccine

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570