19F solid-state NMR approaches to probe antimicrobial peptide interactions with membranes in whole cells.

To address the global problem of bacterial antibiotic resistance, antimicrobial peptides (AMPs) are considered promising therapeutic candidates due to their broad-spectrum and membrane-lytic activity. As preferential interactions with bacteria are crucial, it is equally important to investigate and understand their impact on eukaryotic cells. In this study, we employed 19F solid-state nuclear magnetic resonance (ssNMR) as a novel approach to examine the interaction of AMPs with whole red blood cells (RBCs). We used RBC ghosts (devoid of hemoglobin) and developed a protocol to label their lipid membranes with palmitic acid (PA) monofluorinated at carbon positions 4, 8, or 14 on the acyl chain, allowing us to probe different locations in model and intact RBC ghost membranes. Our work revealed that changes in the 19F chemical shift anisotropy, monitored through a CF bond order parameter (SCF), can provide insights into lipid bilayer dynamics. This information was also obtained using magic-angle spinning 19F ssNMR spectra with and without 1H decoupling, by studying alterations in the second spectral moment (M2) as well as the 19F isotropic chemical shift, linewidth, T1, and T2 relaxation times. The appearance of an additional isotropic peak with a smaller chemical shift anisotropy, a narrower linewidth, and a shorter T1, induced by the AMP caerin 1.1, supports the presence of high-curvature regions in RBCs indicative of pore formation, analogous to its antimicrobial mechanism. In summary, the straightforward incorporation of monofluorinated FAs and rapid signal acquisition offer promising avenues for the study of whole cells using 19F ssNMR.

Hydrofluorination of Alkynes: From (E) to (Z).

The hydrofluorination of alkynes is an efficient synthetic route to monofluoroalkenes or difluoroalkanes. Both fluorinated motifs have found applications in medicinal chemistry and beyond. This review explores the recent advances in the hydrofluorination of diverse alkynes through various activation methods, from classical coinage metal catalysis to metal-free conditions. The range of alkynes goes from the simplest unactivated alkynes to activated ones (ynones and derivatives, ynamides, alkynyl sulfides and sulfones as much as haloalkynes). Regio- and stereoselective methods exists, but there is still room for improvement depending on the type of alkyne.

Exploiting the inductive effect of the trifluoromethyl group: regioselective gold-catalyzed hydration of 2,2,2-trifluoroethyl-substituted alkynes.

The gold-catalyzed hydration of 2,2,2-trifluoroethyl-substituted alkynes is highly regioselective, producing ß-trifluoromethylketones as major products. This transformation illustrates the strong directing effect of the trifluoromethyl group, through its inductive effect, in gold-catalyzed addition to alkynes.

Precision feeding of lactating sows: implementation and evaluation of a decision support system in farm conditions.

Precision feeding (PF) aims to provide the right amount of nutrients at the right time for each animal. Lactating sows generally receive the same diet, which either results in insufficient supply and body reserve mobilization, or excessive supply and high nutrient excretion. With the help of online measuring devices, computational methods, and smart feeders, we introduced the first PF decision support system (DSS) for lactating sows. Precision (PRE) and conventional (STD) feeding strategies were compared in commercial conditions. Every day each PRE sow received a tailored ration that had been computed by the DSS. This ration was obtained by blending a diet with a high AA and mineral content (13.00 g/kg SID Lys, 4.50 g/kg digestible P) and a diet low in AAs and minerals (6.50 g/kg SID Lys, 2.90 g/kg digestible P). All STD sows received a conventional diet (10.08 g/kg SID Lys, 3.78 g/kg digestible P). Before the trial, the DSS was fitted to farm performance for the prediction of piglet average daily gain (PADG) and sow daily feed intake (DFI), with data from 1,691 and 3,712 lactations, respectively. Sow and litter performance were analyzed for the effect of feeding strategy with ANOVA, with results considered statistically significant when P < 0.05. The experiment involved 239 PRE and 240 STD sows. DFI was similarly high in both treatments (PRE: 6.59, STD: 6.45 kg/d; P = 0.11). Litter growth was high (PRE: 2.96, STD: 3.06 kg/d), although it decreased slightly by about 3% in PRE compared to STD treatments (P < 0.05). Sow body weight loss was low, although it was slightly higher in PRE sows (7.7 vs. 2.1 kg, P < 0.001), which might be due to insufficient AA supply in some sows. Weaning to estrus interval (5.6 d) did not differ. In PRE sows SID Lys intake (PRE: 7.7, STD: 10.0 g/kg; P < 0.001) and digestible P intake (PRE: 3.2, STD: 3.8 g/kg; P < 0.001) declined by 23% and 14%, respectively, and feed cost decreased by 12%. For PRE sows, excretion of N and P decreased by 28% and 42%, respectively. According to these results, PF appears to be a very promising strategy for lactating sows.

In lactating sows, nutrient requirements among individual animals vary greatly. With a single diet, lactating sows are likely to be either underfed, which results in body reserve mobilization, or overfed, which results in nutrient excretion. Precision feeding (PF) is a new feeding strategy that aims to provide the right amount of nutrients at the right time for each animal. In this study, we focus on the implementation and the evaluation of a decision support system (DSS) that delivers daily tailored diets to lactating sows. Two experimental treatments were compared: a precision feeding strategy based on the DSS (PRE treatment; 239 sows), and a conventional feeding strategy (STD treatment; 240 sows). Digestible lysine intake and digestible phosphorus intake were reduced by 23% and 14% in PRE sows, respectively, and feed cost by 12%, compared to STD sows. Excretion of nitrogen and phosphorus also decreased for PRE sows by 28% and 42%, respectively. Sow body weight loss was low, although slightly higher in PRE sows, which might be due to insufficient amino acid supply in some sows. PF appears to be a very promising strategy for matching nutrient supply to the specific nutrient requirements of lactating sows.

Gold N-Heterocyclic Carbene Catalysts for the Hydrofluorination of Alkynes Using Hydrofluoric Acid: Reaction Scope, Mechanistic Studies and the Tracking of Elusive Intermediates.

An efficient and chemoselective methodology deploying gold-N-heterocyclic carbene (NHC) complexes as catalysts in the hydrofluorination of terminal alkynes using aqueous HF has been developed. Mechanistic studies shed light on an in situ generated catalyst, formed by the reaction of Brønsted basic gold pre-catalysts with HF in water, which exhibits the highest reactivity and chemoselectivity. The catalytic system has a wide alkyl substituted-substrate scope, and stoichiometric as well as catalytic reactions with tailor-designed gold pre-catalysts enable the identification of various gold species involved along the catalytic cycle. Computational studies aid in understanding the chemoselectivity observed through examination of key mechanistic steps for phosphine- and NHC-coordinated gold species bearing the triflate counterion and the elusive key complex bearing a bifluoride counterion.

Evaluation of a decision support system for precision feeding of gestating sows.

Precision feeding (PF) with the daily mixing of 2 diets with different lysine content (high (H) or low (L)) was previously reported for growing pigs to reduce protein intake and N excretion compared with a conventional feeding (CF) based on a single diet (C). Using a simulation approach based on farm data, the objective of the present paper was to describe and evaluate a decision support system for the PF of gestating sows allowing the daily distribution of a tailored ration to each sow. Two datasets, 1 of 2,511 gestations (farm A) and 1 of 2,528 gestations (farm B), reporting sows' characteristics at insemination and objectives at farrowing were used as inputs for a Python model. This model, mainly based on InraPorc, calculates the nutrient requirements of each sow over gestation and simulates the impact of PF in comparison to CF. Simulated diets L, H, and C contained 3.0, 6.5, and 4.8 g/kg of standardized ileal digestible lysine (SID Lys) and 2.0, 3.3, and 2.5 g/kg of standardized total tract digestible phosphorus (STTD-P), respectively. The influence of farm, parity, gestation week, and their interactions, on calculated SID Lys and STTD-P requirements was analyzed applying a mixed model. The calculated SID Lys and STTD-P requirements increased markedly in the last third of gestation (P < 0.01) and were higher for primiparous than for multiparous sows, unless after week 14 for STTD-P requirement. The calculated SID AA and mineral requirements were lower for farm B than farm A (respectively, 2.94 vs. 3.08 g/kg for SID Lys and 1.30 vs. 1.35 g/kg for STTD-P, P < 0.01). On average, feed L represented 86% and 92% of the feed projected to be delivered by the PF strategy in farms A and B, respectively. Compared to CF, average calculated dietary SID Lys content was lowered by 27% and 32% with PF, for farms A and B, respectively, while average calculated dietary phosphorus content was lowered by 13% and 16%. The simulated proportions of sows in excess and deficient in SID Lys were reduced with PF. Compared to CF, the PF strategy allowed for a 3.6% reduction in simulated feed cost per sow during gestation, and reduced nitrogen and phosphorus intake (by 11.0% and 13.8%, respectively) and excretion (by 16.7% and 15.4%, respectively). To conclude, these simulations indicate that PF of gestating sow appears to be relevant to meet the amino acid requirement while reducing feed cost, and supplies and excretion of nitrogen and phosphorus.

Exploration of individual variability to better predict the nutrient requirements of gestating sows1.

Sows often receive the same feed during gestation even though their nutrient requirements vary during gestation and among sows. The objective of this study was to report the variability in nutrient requirement among sows and during gestation, in order to develop a precision feeding approach. A data set of 2,511 gestations reporting sow characteristics at insemination and their farrowing performance was used as an input for a Python model, adapted from InraPorc, predicting nutrient requirement during gestation. Total metabolizable energy (ME) requirement increased with increasing litter size, gestation weeks, and parity (30.6, 33.6, and 35.5 MJ/d for parity 1, 2, and 3 and beyond, respectively, P < 0.01). Standardized ileal digestible lysine (SID Lys) requirement per kg of diet increased from weeks 1 to 6 of gestation, remained stable from weeks 7 to 10, and increased again from week 11 until the end of gestation (P < 0.01). Average Lys requirement increased with increasing litter size (SID Lys: 3.00, 3.27, 3.50 g/kg for small, medium and large litters, P < 0.01) and decreased when parity increased (SID Lys: 3.61, 3.17, 2.84 g/kg for parity 1, 2, and 3++, P < 0.01). Standardized total tract digestible phosphorus (STTD-P) and total calcium (Total-Ca) requirements markedly increased after week 9, with litter size, and decreased when parity increased (STTD-P: 1.36 vs. 1.31 g/kg for parity 1 and parity 3 and beyond; Total-Ca: 4.28 vs. 4.10 g/kg for parity 1 and parity 3 and beyond, P < 0.01). Based on empirical cumulative distribution functions, a 4-diets strategy, varying in SID Lys and STTD-P content according to parity and gestation period (P1 from weeks 0 to 11, P2 from weeks 12 to 17), may be put forward to meet the requirements of 90% of the sows (2 diets for multiparous sows: P1: 2.8 g SID Lys/kg and 1.1 g STTD-P/kg; P2: 4.5 g SID Lys/kg and 2.3 g STTD-P/kg; and 2 diets for primiparous sows: P1: 3.4 g SID Lys/kg and 1.1g STTD-P/kg; P2: 5.0 g SID Lys/kg, 2.2 g STTD-P/kg). Better considering the high variability of sow requirement should thus make it possible to optimize their performance whilst reducing feeding cost and excretion. Feeding sows closer to their requirement may initially be achieved by grouping and feeding sows according to gestation week and parity, and ultimately by feeding sows individually using a smart feeder allowing the mixing of different feeds differing in their nutrient content.

Gold-Catalyzed Hydrofluorination of Internal Alkynes Using Aqueous HF.

The gold-catalyzed hydrofluorination reaction of internal alkynes using hydrofluoric acid is reported. Notably, those conditions use one of the most economical sources of HF and are free of additional additives. Both symmetrical and unsymmetrical internal alkynes can be utilized, and the use of alkynes bearing a fluorinated group at the propargylic position as substrates allowed for a regioselective hydrofluorination reaction.

Dynamic modeling of nutrient use and individual requirements of lactating sows1.

Nutrient requirements of sows during lactation are related mainly to their milk yield and feed intake, and vary greatly among individuals. In practice, nutrient requirements are generally determined at the population level based on average performance. The objective of the present modeling approach was to explore the variability in nutrient requirements among sows by combining current knowledge about nutrient use with on-farm data available on sows at farrowing [parity, BW, backfat thickness (BT)] and their individual performance (litter size, litter average daily gain, daily sow feed intake) to estimate nutrient requirements. The approach was tested on a database of 1,450 lactations from 2 farms. The effects of farm (A, B), week of lactation (W1: week 1, W2: week 2, W3+: week 3 and beyond), and parity (P1: 1, P2: 2, P3+: 3 and beyond) on sow performance and their nutrient requirements were evaluated. The mean daily ME requirement was strongly correlated with litter growth (R2 = 0.95; P < 0.001) and varied slightly according to sow BW, which influenced the maintenance cost. The mean daily standardized ileal digestible (SID) lysine requirement was influenced by farm, week of lactation, and parity. Variability in SID lysine requirement per kg feed was related mainly to feed intake (R2 = 0.51; P < 0.001) and, to a smaller extent, litter growth (R2 = 0.27; P < 0.001). It was lowest in W1 (7.0 g/kg), greatest in W2 (7.9 g/kg), and intermediate in W3+ (7.5 g/kg; P < 0.001) because milk production increased faster than feed intake capacity did. It was lower for P3+ (6.7 g/kg) and P2 sows (7.3 g/kg) than P1 sows (8.3 g/kg) due to the greater feed intake of multiparous sows. The SID lysine requirement per kg of feed was met for 80% of sows when supplies were 112 and 120% of the mean population requirement on farm A and B, respectively, indicating higher variability in requirements on farm B. Other amino acid and mineral requirements were influenced in the same way as SID lysine. The present modeling approach allows to capture individual variability in the performance of sows and litters according to farm, stage of lactation, and parity. It is an initial step in the development of new types of models able to process historical farm data (e.g., for ex post assessment of nutrient requirements) and real-time data (e.g., to control precision feeding).

[Another way to care for cancer]. / Prendre en charge le cancer autrement.

Seeking to reinforce personalised support for cancer patients, a mobile palliative care team has developed an innovative care facility. The Approche intégrative oncologique (Aion) offers comprehensive and alternative medical care to support patients in an active dimension of the disease. Illustration of these principles with follow-up of a patient called Mr. M.