Adrenal Venous Sampling Using Metanephrine in Primary Aldosteronism With or Without Cortisol Co-Secretion.

Context: The role of plasma metanephrine in adrenal venous sampling (AVS) for assessing lateralization in primary aldosteronism (PA) requires further clarification.

Objective: To evaluate the performance of plasma metanephrine in AVS for determining aldosterone lateralization in PA, with or without mild autonomous cortisol secretion (MACS).

Methods: Sequential AVS under cosyntropin stimulation was conducted in 58 consecutive patients with PA and indication for AVS.

Bystander dermal exposure to drift during pesticide application in vineyards: An experimental factorial study.

Although public concerns about their exposure to agricultural pesticides and the potential impacts on their health began to gain momentum around the early 2000s, there is limited data on the direct exposure of bystanders to spray drift through the deposition of drift droplets on the skin. To address these knowledge gaps in vineyards, trials were conducted on a test bench using artificial vegetation and wind. Different spraying technologies and drift mitigation measures, such as air-induction nozzles or hedgerows along the vineyard margin, were compared.

Impact of Pesticide Training on Safety Climate Perception Among French Cereal Farmers.

The training of farmers in pesticide safety is of prime importance for reducing pesticide use and exposure through the implementation of sustainable management practices. This study aimed to assess the impact of compulsory training on the knowledge and perceptions of cereal farmers, with the help of a safety climate scale. : We approached cereal farmers throughout France during compulsory training and certification procedures for pesticide-related activities.

Guiding antibiotics towards their target using bacteriophage proteins.

Novel therapeutic strategies against difficult-to-treat bacterial infections are desperately needed, and the faster and cheaper way to get them might be by repurposing existing antibiotics. Nanodelivery systems enhance the efficacy of antibiotics by guiding them to their targets, increasing the local concentration at the site of infection. While recently described nanodelivery systems are promising, they are generally not easy to adapt to different targets, and lack biocompatibility or specificity.

Calcineurin inhibitor effects on kidney electrolyte handling and blood pressure: tacrolimus versus voclosporin.

Background: Calcineurin inhibitors (CNIs) affect kidney electrolyte handling and blood pressure (BP) through an effect on the distal tubule. The second-generation CNI voclosporin causes hypomagnesaemia and hypercalciuria less often than tacrolimus. This suggests different effects on the distal tubule, but this has not yet been investigated experimentally.

Safety climate scale for vineyards: an external validity study.

Objectives: Agriculture entered the discussions about safety climates late, despite being one of the most hazardous industries. We recently developed a safety climate scale in Bordeaux vineyards, for which we provided good evidence of reliability and construct validity (Grimbuhler and Viel 2019). In this study, we aimed to establish the external validity of this safety climate scale with the help of an independent national sample of vineyard professionals.

Amide Modifications in the Seed Region of the Guide Strand Improve the On-Target Specificity of Short Interfering RNA.

RNA interference (RNAi) is a well-established research tool and is also maturing as a novel therapeutic approach. For the latter, microRNA-like off-target activity of short interfering RNAs (siRNAs) remains as one of the main problems limiting RNAi drug development. In this communication, we report that replacement of a single internucleoside phosphodiester in the seed region (nucleotides 2 to 7) of the guide strand with an amide linkage suppressed the undesired microRNA-like off-target activity by at least an order of magnitude.

Modular Use of the Uniquely Small Ring A of Mersacidin Generates the Smallest Ribosomally Produced Lanthipeptide.

Mersacidin is an antimicrobial class II lanthipeptide. Lanthipeptides are a class of ribosomally synthesized and post-translationally modified peptides (RiPPs), characterized by intramolecular lanthionine rings. These rings give lanthipeptides their bioactive structure and stability.

Optimization of Automated Synthesis of Amide-Linked RNA.

The recent FDA approval of several antisense and siRNA drugs illustrates the utility of nucleic acid chemical modifications, but numerous challenges remain for generalized nucleic acid therapeutics, urging the exploration of new modification strategies. Replacing backbone phosphates with amides has shown promise for enhancing siRNA activity, specificity, and nuclease resistance; however, amide-linked RNA has not been fully explored due to lengthy and low yielding manual amide coupling procedures. We have addressed this by automating the assembly of amide-linked RNA using an Expedite 8909 nucleic acid synthesizer and optimizing solid-phase synthesis conditions to achieve 91-95% yields in just 5 min of coupling time.

Long-term outcomes and predictors of disabling disease in a population-based cohort of patients with incident Crohn's disease diagnosed between 1994 and 1997.

Background: The identification of early prognostic factors during Crohn's disease (CD) remains needed for physician decision-making to minimize structural bowel damage, which this study aimed to assess in a population-based setting.

Methods: All incident cases of CD were prospectively registered from 1994 to 1997 in Brittany, a limited area of France. All charts of patients were reviewed from the diagnosis to the last clinic visit in 2015.

Mutational Studies of the Mersacidin Leader Reveal the Function of Its Unique Two-Step Leader Processing Mechanism.

The class II lanthipeptide mersacidin, a ribosomally synthesized and post-translationally modified peptide (RiPP), displays unique intramolecular structures, including a very small lanthionine ring. When applied in the growing field of RiPP engineering, these can add unique features to new-to-nature compounds with novel properties. Recently, a heterologous expression system for mersacidin in was developed to add its modification enzymes to the RiPP engineering toolbox and further explore mersacidin biosynthesis and leader-processing.

Inverse probability weighting to handle attrition in cohort studies: some guidance and a call for caution.

Background: Attrition in cohort studies challenges causal inference. Although inverse probability weighting (IPW) has been proposed to handle attrition in association analyses, its relevance has been little studied in this context. We aimed to investigate its ability to correct for selection bias in exposure-outcome estimation by addressing an important methodological issue: the specification of the response model.

Characterization of Leader Processing Shows That Partially Processed Mersacidin Is Activated by AprE After Export.

The ribosomally synthesized and post-translationally modified peptide mersacidin is a class II lanthipeptide with good activity against Gram-positive bacteria. The intramolecular lanthionine rings, that give mersacidin its stability and antimicrobial activity, are specific structures with potential applications in synthetic biology. To add the mersacidin modification enzymes to the synthetic biology toolbox, a heterologous expression system for mersacidin in has recently been developed.

Semisynthetic Macrocyclic Lipo-lanthipeptides Display Antimicrobial Activity Against Bacterial Pathogens.

A large number of antimicrobial peptides depend on intramolecular disulfide bonds for their biological activity. However, the relative instability of disulfide bonds has limited the potential of some of these peptides to be developed into therapeutics. Conversely, peptides containing intramolecular (methyl)lanthionine-based bonds, lanthipeptides, are highly stable under a broader range of biological and physical conditions.

Heterologous Expression of Mersacidin in Elucidates the Mode of Leader Processing.

The lanthipeptide mersacidin is a ribosomally synthesized and post-translationally modified peptide (RiPP) produced by . It has antimicrobial activity against a range of Gram-positive bacteria, including methicillin-resistant , giving it potential therapeutic relevance. The structure and bioactivity of mersacidin are derived from a unique combination of lanthionine ring structures, which makes mersacidin also interesting from a lantibiotic-engineering point of view.

Retrospective assessment of pregnancy exposure to particulate matter from desert dust on a Caribbean island: could satellite-based aerosol optical thickness be used as an alternative to ground PM concentration?

Desert dust transported from the Saharan-Sahel region to the Caribbean Sea is responsible for peak exposures of particulate matter (PM). This study explored the potential added value of satellite aerosol optical thickness (AOT) measurements, compared to the PM concentration at ground level, to retrospectively assess exposure during pregnancy. MAIAC MODIS AOT retrievals in blue band (AOT) were extracted for the French Guadeloupe archipelago.

Heat Stress and Cardiac Strain in French Vineyard Workers.

Agricultural workers often produce considerable excess heat due to the physically demanding nature of their activities, increasing their risk of thermal stress in even moderately warm conditions. Few studies have examined the physiological responses to heat load in agriculture. We aimed to assess the heat strain experienced by vineyard workers during canopy management in dry field conditions, and to disentangle the effects of the heat produced by the body and the thermal environment.

Conjugation of Synthetic Polyproline Moietes to Lipid II Binding Fragments of Nisin Yields Active and Stable Antimicrobials.

Coupling functional moieties to lantibiotics offers exciting opportunities to produce novel derivatives with desirable properties enabling new functions and applications. Here, five different synthetic hydrophobic polyproline peptides were conjugated to either nisin AB (the first two rings of nisin) or nisin ABC (the first three rings of nisin) by using click chemistry. The antimicrobial activity of nisin ABC + O6K3 against decreased 8-fold compared to full-length nisin, but its activity was 16-fold better than nisin ABC, suggesting that modifying nisin ABC is a promising strategy to generate semi-synthetic nisin hybrids.

Rapid and Selective Chemical Editing of Ribosomally Synthesized and Post-Translationally Modified Peptides (RiPPs) via Cu -Catalyzed β-Borylation of Dehydroamino Acids.

We report the fast and selective chemical editing of ribosomally synthesized and post-translationally modified peptides (RiPPs) by β-borylation of dehydroalanine (Dha) residues. The thiopeptide thiostrepton was modified efficiently using Cu -catalysis under mild conditions and 1D/2D NMR of the purified product showed site-selective borylation of the terminal Dha residues. Using similar conditions, the thiopeptide nosiheptide, lanthipeptide nisin Z, and protein SUMO_G98Dha were also modified efficiently.

New developments in RiPP discovery, enzymology and engineering.

Covering: up to June 2020Ribosomally-synthesized and post-translationally modified peptides (RiPPs) are a large group of natural products. A community-driven review in 2013 described the emerging commonalities in the biosynthesis of RiPPs and the opportunities they offered for bioengineering and genome mining. Since then, the field has seen tremendous advances in understanding of the mechanisms by which nature assembles these compounds, in engineering their biosynthetic machinery for a wide range of applications, and in the discovery of entirely new RiPP families using bioinformatic tools developed specifically for this compound class.

Synthesis and Characterization of Heterodimers and Fluorescent Nisin Species by Incorporation of Methionine Analogues and Subsequent Click Chemistry.

Noncanonical amino acids form a highly diverse pool of building blocks that can render unique physicochemical properties to peptides and proteins. Here, four methionine analogues with unsaturated and varying side chain lengths were successfully incorporated at four different positions in nisin in through force feeding. This approach allows for residue-specific incorporation of methionine analogues into nisin to expand their structural diversity and alter their activity profiles.