Molecular basis for the wide range of affinity found in Csr/Rsm protein-RNA recognition

The carbon storage regulator/regulator of secondary metabolism (Csr/Rsm) type of small non-coding RNAs (sRNAs) is widespread throughout bacteria and acts by sequestering the global translation repressor protein CsrA/RsmE from the ribosome binding site of a subset of mRNAs. Although we have previously described the molecular basis of a high affinity RNA target bound to RsmE, it remains unknown how other lower affinity targets are recognized by the same protein. Here, we have determined the nuclear magnetic resonance solution structures of five separate GGA binding motifs of the sRNA RsmZ of Pseudomonas fluorescens in complex with RsmE. The structures explain how the variation of sequence and structural context of the GGA binding motifs modulate the binding affinity for RsmE by five orders of magnitude (∼10 nM to ∼3 mM, Kd). Furthermore, we see that conformational adaptation of protein side-chains and RNA enable recognition of different RNA sequences by the same protein contributing to binding affinity without conferring specificity. Overall, our findings illustrate how the variability in the Csr/Rsm protein-RNA recognition allows a fine-tuning of the competition between mRNAs and sRNAs for the CsrA/RsmE protei

Personalized bacteriophage therapy outcomes for 100 consecutive cases:a multicentre, multinational, retrospective observational study

In contrast to the many reports of successful real-world cases of personalized bacteriophage therapy (BT), randomized controlled trials of non-personalized bacteriophage products have not produced the expected results. Here we present the outcomes of a retrospective observational analysis of the first 100 consecutive cases of personalized BT of difficult-to-treat infections facilitated by a Belgian consortium in 35 hospitals, 29 cities and 12 countries during the period from 1 January 2008 to 30 April 2022. We assessed how often personalized BT produced a positive clinical outcome (general efficacy) and performed a regression analysis to identify functional relationships. The most common indications were lower respiratory tract, skin and soft tissue, and bone infections, and involved combinations of 26 bacteriophages and 6 defined bacteriophage cocktails, individually selected and sometimes pre-adapted to target the causative bacterial pathogens. Clinical improvement and eradication of the targeted bacteria were reported for 77.2% and 61.3% of infections, respectively. In our dataset of 100 cases, eradication was 70% less probable when no concomitant antibiotics were used (odds ratio = 0.3; 95% confidence interval = 0.127–0.749). In vivo selection of bacteriophage resistance and in vitro bacteriophage–antibiotic synergy were documented in 43.8% (7/16 patients) and 90% (9/10) of evaluated patients, respectively. We observed a combination of antibiotic re-sensitization and reduced virulence in bacteriophage-resistant bacterial isolates that emerged during BT. Bacteriophage immune neutralization was observed in 38.5% (5/13) of screened patients. Fifteen adverse events were reported, including seven non-serious adverse drug reactions suspected to be linked to BT. While our analysis is limited by the uncontrolled nature of these data, it indicates that BT can be effective in combination with antibiotics and can inform the design of future controlled clinical trials. BT100 study, ClinicalTrials.gov registration: NCT05498363.</p

Indicators for Evaluation of Energetic Performance of Net Zero Energy Buildings

International audienc

A Comparison of Direct and Indirect Flexibilities on the Self-Consumption of an Office Building: The Case of Predis-MHI, a Smart Office Building

International audienceThe purpose of this paper is to provide a method for assessing the impact of direct and indirect flexibilities on the self-consumption of office buildings. The goal is to assess how both the human actors and technical interventions can affect or mitigate deviations in the self-consumption level of a building from its optimal. This paper considers the Predis-MHi platform (a living lab) as a representative case study and applies a Mixed Integer Linear Programming optimization to manage both the direct (stationary battery charging) and indirect flexibilities (Electric Vehicle charging when users plug and unplug their vehicles). Our results indicate that the potential for a building’s self-consumption improvement using indirect flexibilities does exist and can be quantified. However, this type of flexibility is highly dependent on human actors which presents a high level of uncertainty and is difficult to account for in all stages of a building’s development and use. Direct flexibilities such as stationary battery storage can be used to mitigate the undesired effects of having significant levels of indirect flexibilities on a tertiary sector building’s energy performance. The results from this study could potentially be modeled into an indicator, which would serve to influence occupant behavior towards a desired optimal

Electropolymerization of copolymer electrolyte into titania nanotube electrodes for high-performance 3D microbatteries

It is described the electrochemical synthesis of a copolymer electrolyte (PMMA-PEO) into titania nanotubes. The electrochemical cell based on copolymer electrolyte and titania nanotube electrode reveals high performances opening new perspectives for the fabrication of 3D hybrid Li-ion microbatteries prepared solely by electrochemical techniques

Electrodeposited copolymer electrolyte into nanostructured titania electrodes for 3D Li-ion microbatteries

The electrochemical synthesis of a copolymer electrolyte (PEO-PMMA) into titania nanotubes is described and studied. Compared with the electrochemical systems based on solid electrolytes deposited by top-down techniques, the copolymer/titania nanotube material reveals high electrochemical performance, opening new perspectives for the fabrication of 3D all-solid-state microbatteries

Molecular basis for the wide range of affinity found in Csr/Rsm protein-RNA recognition

The carbon storage regulator/regulator of secondary metabolism (Csr/Rsm) type of small non-coding RNAs (sRNAs) is widespread throughout bacteria and acts by sequestering the global translation repressor protein CsrA/RsmE from the ribosome binding site of a subset of mRNAs. Although we have previously described the molecular basis of a high affinity RNA target bound to RsmE, it remains unknown how other lower affinity targets are recognized by the same protein. Here, we have determined the nuclear magnetic resonance solution structures of five separate GGA binding motifs of the sRNA RsmZ of Pseudomonas fluorescens in complex with RsmE. The structures explain how the variation of sequence and structural context of the GGA binding motifs modulate the binding affinity for RsmE by five orders of magnitude (∼10 nM to ∼3 mM, Kd). Furthermore, we see that conformational adaptation of protein side-chains and RNA enable recognition of different RNA sequences by the same protein contributing to binding affinity without conferring specificity. Overall, our findings illustrate how the variability in the Csr/Rsm protein–RNA recognition allows a fine-tuning of the competition between mRNAs and sRNAs for the CsrA/RsmE protein.ISSN:1362-4962ISSN:0301-561

Towards a Digital Twin of Grenoble-Presqu'île: A Framework for District-Scale Digital Twin Development

International audienc

Pectin-Derived Acidic Oligosaccharides Improve the Outcome of Pseudomonas aeruginosa Lung Infection in C57BL/6 Mice.

The administration of prebiotics as oligosaccharides (OS), by acting on intestinal microbiota, could modulate the immune and inflammatory response and represent a new strategy to improve the outcome of bacterial infection. The aim of this study was to determine whether pectin-derived acidic oligosaccharides (pAOS) could modulate the outcome of pulmonary P. aeruginosa (PA) infection in C57BL/6 mice, which develop a Th1 response to PA lung infection. Mice were randomized for 5 weeks to consume a control or a 5% pAOS diet and chronically infected by PA. Resistance to a second PA infection was also analyzed by reinfecting the surviving mice 2 weeks after the first infection. Compared with control mice, mice fed pAOS had reduced mortality (P<0.05). This improvement correlated with a better control of the inflammatory response with a lower neutrophil count on day 1 (P<0.05), a sustained neutrophil and macrophage recruitment on days 2 and 3 (P<0.01) a greater and sustained IL-10 release in lung (P<0.05) and a reduction of the Th1 response and M1 activation with a lower IFN-γ/IL-4 (P<0.01) and nos2/arg1 (P<0.05) ratios. These results coincided with a modulation of the intestinal microbiota as shown by an increased butyric acid concentration in feces (P<0.05). Moreover, pAOS decreased the bacterial load (P<0.01) in mice reinfected 2 weeks after the first infection, suggesting that pAOS could reduce pulmonary exacerbations. In conclusion, pAOS improved the outcome of PA infection in C57BL/6 mice by modulating the intestinal microbiota and the inflammatory and immune responses

An Assessment of Energy Flexibility Solutions from the Perspective of Low-Tech

International audienceThe energy transition is a multidisciplinary challenge that warrants solutions that are robust and sustainable. Energy flexibility, one of the key pillars of the energy transition, is an umbrella term that covers multiple innovative solutions implemented at all levels of the electric grid to ensure power quality standards, amongst other objectives. Low-tech, on the other hand, emphasizes designing, producing, and sustainably implementing solutions. Therefore, considering the multidisciplinary nature of energy transition and the existing energy flexibility solutions, the purpose of this research work is multilateral: first, it presents the concept of low-tech and its associated mechanisms; then, it addresses the misconceptions and similarities that low-tech might have with other innovation approaches; and finally, it provides an assessment of existing flexibility solutions using low-tech as a tool. The result of this assessment is presented qualitatively and indicates that indirect energy flexibility solutions rank higher on a low-tech scale relative to supply-side energy flexibility solutions and energy storage flexibility solutions