Les tentatives d’encadrement des discours écrits des députés sous la Restauration : l’art oratoire magnifié ?

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Crude and acid oils from olive pomace as alternative fat sources in growing-finishing pigs

The inclusion of crude and acid oils from olive pomace can lead to more unsaturated meat products and, especially in the case of olive pomace acid oil, achieve a more economically and environmentally sustainable swine production. The objective of this trial was to study the effect of dietary supplementation with crude and acid oils from olive pomace, which are rich in monounsaturated fatty acids (FAs) and have differing free FA content, on growth performance, digestibility, carcass parameters and FA profile of Longissimus muscle (LM) and backfat in growing-finishing pigs compared to the conventional crude palm oil. A total of 224 male and female pigs [(Landrace × Large White) × Duroc] were randomly distributed into 48 pens according to initial BW (58.7 ± 9.71 kg, mean ± SD) and sex. Four experimental treatments were randomly assigned (n = 12 pens/treatment; 4-5 pigs/pen) for the growing (0-42 days) and finishing (40-62 days) phases. Treatments consisted of a basal diet supplemented with 5% (as-fed basis) palm oil (PO), olive pomace oil (O), olive pomace acid oil (OA) or a mixture (M) of PO and OA at 50/50. No differences were found in the growth performance results between PO, O or M, but animals fed OA showed a lower gain to feed ratio than M (P = 0.008). No differences were found in apparent ileal digestibility among treatments, however, animals fed O and OA showed the highest values of total FA apparent total tract digestibility, while those fed PO had the lowest values, and M had intermediate values (P < 0.001). No differences were observed in carcass composition among treatments. In relation to backfat and the LM FA profile, O and OA treatments led to a higher unsaturated FA to saturated FA ratio and a lower content in saturated FA than PO. Moreover, O showed a higher intramuscular fat (IMF) content in LM than PO (P = 0.037). It is concluded that olive pomace oil is an interesting alternative fat source that can be included at 5% in growing-finishing pig diets, leading to meat products with more IMF, rich in monounsaturated FA, reaching high FA digestibility values and good pig performance parameters. Alternatively, olive pomace acid oil blended with conventional palm oil did not negatively impact fat utilisation nor performance. Including these fat by-products reduced feeding costs and led to a more efficient and environmentally sustainable production

Olive pomace oil and acid oil as alternative fat sources in growing-finishing broiler chicken diets

The aim of the present study was to investigate the effect of dietary supplementation of olive pomace oil and olive pomace acid oil, which are rich in monounsaturated fatty acids (FA) but differ in free FA content, on growth performance, digestibility and FA profile of abdominal fat and breast meat. A total of 3,048 one-day-old mixed-sex broiler chickens (Ross 308) were randomly distributed into 24 pens and 3 dietary treatments (8 replicates per treatment). Experimental diets were administered for growing (from 22 to 29 d) and finishing (from 30 to 39 d) periods, consisting of a basal diet supplemented with 6% (as-fed basis) palm oil (PO), olive pomace oil (O), or olive pomace acid oil (OA). Animals fed O achieved the lowest feed conversion ratio (P < 0.01), together with the highest AME value (P = 0.003), but no differences were observed between OA and PO. Regarding FA digestibility, O and OA showed higher values than PO for all FA in both apparent ileal digestibility (AID) and apparent total tract digestibility. Comparing the AID between O and OA, no differences were observed for total FA, monounsaturated FA, or polyunsaturated FA, but animals fed OA showed lower AID values for saturated FA than those fed O (P < 0.001). The FA profile of abdominal fat and breast meat reflected that of the diet, with higher monounsaturated FA and lower saturated FA in animals fed O and OA compared to those fed PO. In sum, the inclusion of both olive pomace oil and acid oil in growing-finishing broiler chicken diets led to great performance parameters and high FA digestibility values, together with an enrichment with monounsaturated FA in abdominal fat and breast meat compared to the use of palm oil. However, a better AID of saturated FA and feed conversion ratio is achieved with O compared to OA

Olive pomace oil and acid oil as alternative fat sources in growing-finishing broiler chicken diets

The aim of the present study was to investigate the effect of dietary supplementation of olive pomace oil and olive pomace acid oil, which are rich in monounsaturated fatty acids (FA) but differ in free FA content, on growth performance, digestibility and FA profile of abdominal fat and breast meat. A total of 3,048 one-day-old mixed-sex broiler chickens (Ross 308) were randomly distributed into 24 pens and 3 dietary treatments (8 replicates per treatment). Experimental diets were administered for growing (from 22 to 29 d) and finishing (from 30 to 39 d) periods, consisting of a basal diet supplemented with 6% (as-fed basis) palm oil (PO), olive pomace oil (O), or olive pomace acid oil (OA). Animals fed O achieved the lowest feed conversion ratio (P < 0.01), together with the highest AME value (P = 0.003), but no differences were observed between OA and PO. Regarding FA digestibility, O and OA showed higher values than PO for all FA in both apparent ileal digestibility (AID) and apparent total tract digestibility. Comparing the AID between O and OA, no differences were observed for total FA, monounsaturated FA, or polyunsaturated FA, but animals fed OA showed lower AID values for saturated FA than those fed O (P < 0.001). The FA profile of abdominal fat and breast meat reflected that of the diet, with higher monounsaturated FA and lower saturated FA in animals fed O and OA compared to those fed PO. In sum, the inclusion of both olive pomace oil and acid oil in growing-finishing broiler chicken diets led to great performance parameters and high FA digestibility values, together with an enrichment with monounsaturated FA in abdominal fat and breast meat compared to the use of palm oil. However, a better AID of saturated FA and feed conversion ratio is achieved with O compared to OA

Binding site plasticity in viral PPxY Late domain recognition by the third WW domain of human NEDD4

The recognition of PPxY viral Late domains by the third WW domain of the HECT-E3 ubiquitin ligase NEDD4 (hNEDD4-WW3) is essential for the completion of the budding process of numerous enveloped viruses, including Ebola, Marburg, HTLV1 or Rabies. hNEDD4-WW3 has been validated as a promising target for the development of novel host-oriented broad spectrum antivirals. Nonetheless, finding inhibitors with good properties as therapeutic agents remains a challenge since the key determinants of binding affinity and specificity are still poorly understood. We present here a detailed structural and thermodynamic study of the interactions of hNEDD4-WW3 with viral Late domains combining isothermal titration calorimetry, NMR structural determination and molecular dynamics simulations. Structural and energetic differences in Late domain recognition reveal a highly plastic hNEDD4-WW3 binding site that can accommodate PPxY-containing ligands with varying orientations. These orientations are mostly determined by specific conformations adopted by residues I859 and T866. Our results suggest a conformational selection mechanism, extensive to other WW domains, and highlight the functional relevance of hNEDD4-WW3 domain conformational flexibility at the binding interface, which emerges as a key element to consider in the search for potent and selective inhibitors of therapeutic interest.This research has been financed by grants BIO2009-13261-C02, BIO2012-39922-CO2 and BIO2016-78746-C2-1-R from the Spanish Ministry of Education and Science (I.L.) including AEI/FEDER EU funds, by CTQ2017-83810-R grant (F.J.B) and by BFU2014-53787-P, the IRB Barcelona and the BBVA Foundation (M.J.M)

Phage display identification of nanomolar ligands for human NEDD4-WW3: Energetic and dynamic implications for the development of broad-spectrum antivirals

This research has been financed by grants BIO2016-78746-C2-1-R and PID2020-112895RB-100 from the Spanish Ministry of Education and Science (I.L.) including AEI/FEDER EU funds. R.N.H. was funded in part by National Institutes of Health grants AI138052 and AI138630. M. I.B. and J.M.C. were recipients of a research contract from the Spanish Ministry of Education and Science. F.C. was funded by a predoctoral fellowship from the Andalusian Government P10-CVI-5915. J.M.C. ac-knowledges a reincorporation research contract from the University of Granada. We thank Dr. Sachdev Sidhu for his invaluable assistance setting up the phage display techniques in our laboratory. We also thank the support of the C.I.C. of the University of Granada.The recognition of PPxY viral Late domains by the third WW domain of the human HECT-E3 ubiquitin ligase NEDD4 (NEDD4-WW3) is essential for the budding of many viruses. Blocking these interactions is a promising strategy to develop broad-spectrum antivirals. As all WW domains, NEDD4-WW3 is a challenging therapeutic target due to the low binding affinity of its natural interactions, its high conformational plasticity, and its complex thermodynamic behavior. In this work, we set out to investigate whether high affinity can be achieved for monovalent ligands binding to the isolated NEDD4-WW3 domain. We show that a competitive phage-display set-up allows for the identification of high-affinity peptides showing inhibitory activity of viral budding. A detailed biophysical study combining calorimetry, nuclear magnetic resonance, and molecular dynamic simulations reveals that the improvement in binding affinity does not arise from the establishment of new interactions with the domain, but is associated to conformational restrictions imposed by a novel C-terminal -LFP motif in the ligand, unprecedented in the PPxY interactome. These results, which highlight the complexity of WW domain interactions, provide valuable insight into the key elements for high binding affinity, of interest to guide virtual screening campaigns for the identification of novel therapeutics targeting NEDD4-WW3 interactions.Spanish Government BIO2016-78746-C2-1-R PID2020-112895RB-100 AEI/FEDER EU funds AI138052 AI138630United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA P10-CVI-5915German Research Foundation (DFG)University of Granad

Differential regulation of immune responses and macrophage/neuron interactions in the dorsal root ganglion in young and adult rats following nerve injury

Background: Neuropathic pain is an apparently spontaneous experience triggered by abnormal physiology of the peripheral or central nervous system, which evolves with time. Neuropathic pain arising from peripheral nerve injury is characterized by a combination of spontaneous pain, hyperalgesia and allodynia. There is no evidence of this type of pain in human infants or rat pups; brachial plexus avulsion, which causes intense neuropathic pain in adults, is not painful when the injury is sustained at birth. Since infants are capable of nociception from before birth and display both acute and chronic inflammatory pain behaviour from an early neonatal age, it appears that the mechanisms underlying neuropathic pain are differentially regulated over a prolonged postnatal period.Results: We have performed a microarray analysis of the rat L4/L5 dorsal root ganglia (DRG), 7 days post spared nerve injury, a model of neuropathic pain. Genes that are regulated in adult rats displaying neuropathic behaviour were compared to those regulated in young rats (10 days old) that did not show the same neuropathic behaviour. The results show a set of genes, differentially regulated in the adult DRG, that are principally involved in immune system modulation. A functional consequence of this different immune response to injury is that resident macrophages cluster around the large A sensory neuron bodies in the adult DRG seven days post injury, whereas the macrophages in young DRG remain scattered evenly throughout the ganglion, as in controls.Conclusions: The results show, for the first time, a major difference in the neuroimmune response to nerve injury in the dorsal root ganglion of young and adult rats. Differential analysis reveals a new set of immune related genes in the ganglia, that are differentially regulated in adult neuropathic pain, and that are consistent with the selective activation of macrophages around adult, but not young large A sensory neurons post injury. These differences may contribute to the reduced incidence of neuropathic pain in infants