La Raça bovina Bruna dels Pirineus : qualitat de la canal i de la carn : característiques bioquímiques del múscul longissimus thoracis en set races autòctones

L'objectiu principal d'aquesta tesi és la caracterització de la raça bovina Bruna dels Pirineus per tal de conèixer, per una banda, la variabilitat de la raça en relació a la qualitat de la canal, la qualitat de la carn i les característiques bioquímiques del múscul longissimus thoracis (pigments hemo, percentatge de miosina MHC I mitjançant ELISA i activitats enzimàtiques lactat deshidrogenasa i isocitrat deshidrogenasa) i, per l'altra, l'estudi de les seves relacions amb les variables o atributs de l'anàlisi sensorial (olor de vedella, olor de fetge, flavor de vedella, flavor de fetge, tendresa i sucositat), a fi de poder avaluar objectivament el potencial d'aquesta raça. Un total de 74 vedells mascles de la raça Bruna dels Pirineus (provinents de 22 ramaders i engreixats al llarg dels anys 1996-98) van ser deslletats als 7 mesos de mitjana d'edat i amb un pes mitjà de 268 kg. L'alimentació del període d'engreix (171 dies de mitjana) va ser ad libitum, amb una dieta exclusivament vegetal, a base de pinso concentrat i suplementada amb farratge. El pes viu de sacrifici dels animals fou de 541,3 ±29,6 kg, amb una edat mitjana de 380,6 ±34,4 dies. A més a més, també s'estudia l'efecte raça-sistema de producció sobre el color i les característiques bioquímiques del múscul longissimus thoracis (LT) en set races autòctones espanyoles de vacum de carn amb un total de 478 vedells mascles repartits de la manera següent: 70 de l' Asturiana de los Valles (AV), 70 de l' Asturiana de la Montaña (AM), 55 de la Pirenaica (PI), 74 de la Bruna dels Pirineus (BP), 71 de l' Avileña-Negra Ibérica (A-NI), 70 de la Morucha (MO) i 68 de la Retinta (RE). Els vedells es van criar amb les mares en sistema extensiu fins a l'inici del període d'engreix (entre 5 i 7 mesos), el qual va consistir en una alimentació ad libitum i d'acord amb el sistema de producció característic de cada raça. La mitjana d'edat de sacrifici de les diferents races va oscil·lar entre els 363 i els 541dies, mentre que el pes canal es va moure entre els 250 i 334,5 kg. S'observà un efecte significatiu del raça-sistema de producció sobre el color i les característiques bioquímiques del múscul LT.The main objective of this study was the characterisation of the Bruna dels Pirineus cattle breed in relation to carcass quality, meat quality and longissimus thoracis (LT) biochemical characteristics variability (haem pigments, myosin MHC I percentage, lactate dehydrogenase and isocitrate dehydrogenase activities), and furthermore, to examine their relationships with the sensory analysis variables (beef and livery odour intensity, beef and livery flavour intensity, tenderness and juiciness), in order to evaluate the potential of this breed. A total of 74 young bulls of the Bruna dels Pirineus Breed (from 22 herds and reared along 1996-98) were used. Calves were weaned at about 7 months old, with an average weaning-weight of 286 kg, and fed ad libitum with an exclusively vegetal diet (concentrate and supplemented with hay) during 171 days, on average. Live weight at sacrifice was 541.3 ±29.6 kg, with an average age of 380.6 ±34.4 days. Additionally, the effect of the breed-production system on the colour and the biochemical characteristics of LT muscle in seven local Spanish beef cattle breeds was studied (478 young bulls): 70 from Asturiana de los Valles (AV), 70 from Asturiana de la Montaña (AM), 55 from Pirenaica (PI), 74 from Bruna dels Pirineus (BP), 71 from Avileña-Negra Ibérica (A-NI), 70 from Morucha (MO) and 68 from Retinta (RE). Calves were reared in an extensive regime together with their mothers and started fattening at about 5 to 7 months old. They were fed a breed-specific diet ad libitum. The ingredients always had a vegetable origin. Age at slaughter was between 363 and 541 days; and carcass weight between 250 and 334.5 kg. Significant differences between breed-production systems were found for all the traits evaluated

Allosteric Modulation of NMDARs Reverses Patients' Autoantibody Effects in Mice

Background and Objectives To demonstrate that an analog (SGE-301) of a brain-derived cholesterol metabolite, 24(S)- hydroxycholesterol, which is a selective positive allosteric modulator (PAM) of NMDA re- ceptors (NMDARs), is able to reverse the memory and synaptic alterations caused by CSF from patients with anti-NMDAR encephalitis in an animal model of passive transfer of antibodies. Methods Four groups of mice received (days 1-14) patients' or controls' CSF via osmotic pumps connected to the cerebroventricular system and from day 11 were treated with daily sub- cutaneous injections of SGE-301 or vehicle (no drug). Visuospatial memory, locomotor activity (LA), synaptic NMDAR cluster density, hippocampal long-term potentiation (LTP), and paired-pulse facilitation (PPF) were assessed on days 10, 13, 18, and 26 using reported techniques. Results On day 10, mice infused with patients' CSF, but not controls' CSF, presented a significant visuospatial memory deficit, reduction of NMDAR clusters, and impairment of LTP, whereas LA and PPF were unaffected. These alterations persisted until day 18, the time of maximal deficits in this model. In contrast, mice that received patients' CSF but from day 11 were treated with SGE-301 showed memory recovery (day 13), and on day 18, all paradigms (memory, NMDAR clusters, and LTP) had reversed to values similar to those of controls. On day 26, no differences were observed among experimental groups. Discussion An oxysterol biology-based PAM of NMDARs is able to reverse the synaptic and memory deficits caused by CSF from patients with anti-NMDAR encephalitis. These findings suggest a novel adjuvant treatment approach that deserves future clinical evaluation

Allosteric modulation of NMDA receptors prevents the antibody effects of patients with anti-NMDAR encephalitis

Anti-N-Methyl-D-Aspartate Receptor (NMDAR) encephalitis is an immune-mediated disease characterized by a complex neuropsychiatric syndrome in association with an antibody-mediated decrease of NMDAR. About 85% of patients respond to immunotherapy (and removal of an associated tumor if it applies), but it often takes several months or more than 1 year for patients to recover. There are no complementary treatments, beyond immunotherapy, to accelerate this recovery. Previous studies showed that SGE-301, a synthetic analog of 24(S)-hydroxycholesterol, which is a potent, and selective positive allosteric modulator of NMDAR, reverted the memory deficit caused by phencyclidine (a non-competitive antagonist of NMDAR), and prevented the NMDAR dysfunction caused by patients' NMDAR antibodies in cultured neurons. An advantage of SGE-301 is that it is optimized for systemic delivery such that plasma and brain exposures are sufficient to modulate NMDAR activity. Here, we used SGE-301 to confirm that in cultured neurons it prevented the antibody-mediated reduction of receptors, and then we applied it to a previously reported mouse model of passive cerebroventricular transfer of patients' CSF antibodies. Four groups were established: mice receiving continuous (14-day) infusion of patients' or controls' CSF, treated with daily subcutaneous administration of SGE-301 or vehicle (no drug). The effects on memory were examined with the novel object location (NOL) test at different time points, and the effects on synaptic levels of NMDAR (assessed with confocal microscopy) and plasticity (long-term potentiation [LTP]) were examined in the hippocampus on day 18, which in this model corresponds to the last day of maximal clinical and synaptic alterations. As expected, mice infused with patients' CSF antibodies, but not those infused with controls' CSF, and treated with vehicle developed severe memory deficit without locomotor alteration, accompanied by a decrease of NMDAR clusters and impairment of LTP. All antibody-mediated pathogenic effects (memory, synaptic NMDAR, LTP) were prevented in the animals that were treated with SGE-301, despite that this compound did not antagonize antibody binding. Additional investigations on the potential mechanisms related to these SGE-301 effects showed that (1) in cultured neurons SGE-301 prolonged the decay time of NMDAR-dependent spontaneous excitatory postsynaptic currents suggesting a prolonged open time of the channel, and (2) it significantly decreased the internalization of antibody-bound receptors suggesting that additional, yet unclear mechanisms, contribute in keeping unchanged the surface NMDAR density. Overall, these findings suggest that SGE-301, or similar modulators of NMDAR, could potentially serve as complementary treatment for anti-NMDAR encephalitis and deserve future investigations

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Effect of reducing and replacing pork fat on the physicochemical, instrumental and sensory characteristics throughout storage time of small caliber non-acid fermented sausages with reduced sodium content

The effect of pork fat reduction (from 44% to 20% final fat content) and its partial substitution by sunflower oil (3% addition) on the physicochemical, instrumental and sensory properties throughout storage time of small caliber non-acid fermented sausages (fuet type) with reduced sodium content (with partial substitution of NaCl by KCl and K-lactate) and without direct addition of nitrate and nitrite (natural nitrate source used instead), was studied. Results showed that sausages with reduced fat (10% initial fat content) and with acceptable sensory characteristics can be obtained by adding to the shoulder lean (8% fat content) during the grinding, either 3.3% backfat (3% fat content) or 3% sunflower oil, both previously finely comminuted with lean. Furthermore, sunflower oil showed to be suitable for partial pork backfat substitution in very lean fermented sausages, conferring desirable sensory properties similar to those of sausages with standard fat content. The sensory quality of the sausages was maintained after three-month cold storage in modified atmosphere

Technologies de procédé et de contrôle pour réduire la teneur en sel du jambon sec et des saucissons

Dans certains pays européens, les produits carnés élaborés peuvent représenter près de 20% de la consommation journalière de sodium. De ce fait, les industries de la viande tentent de réduire la teneur en sel dans les produits carnés pour répondre, d’une part aux attentes des consommateurs et d’autre part aux demandes des autorités sanitaires. Le système Quick‐Dry‐Slice process (QDS®), couplé avec l’utilisation de sels substituant le chlorure de sodium (NaCl), a permis de fabriquer, avec succès, des saucisses fermentées à basse teneur en sel en réduisant le cycle de fabrication et sans ajout de NaCl supplémentaire. Les technologies de mesure en ligne non destructives, comme les rayons X et l’induction électromagnétique, permettent de classifier les jambons frais suivant leur teneur en gras, un paramètre crucial pour adapter la durée de l’étape de salaison. La technologie des rayons X peut aussi être utilisée pour estimer la quantité de sel incorporée pendant la salaison. L’information relative aux teneurs en sel et en gras est importante pour optimiser le processus d’élaboration du jambon sec en réduisant la variabilité de la teneur en sel entre les lots et dans un même lot, mais aussi pour réduire la teneur en sel du produit final. D’autres technologies comme la spectroscopie en proche infrarouge (NIRS) ou spectroscopie microondes sont aussi utiles pour contrôler le processus d’élaboration et pour caractériser et classifier les produits carnés élaborés, selon leur teneur en sel. La plupart de ces technologies peuvent être facilement appliquées en ligne dans l’industrie afin de contrôler le processus de fabrication et d’obtenir ainsi des produits carnés présentant les caractéristiques recherchées.In some European countries, processed meat products can contribute up to 20% of the sodium intake of the diet. Therefore, meat industries are interested in reducing the salt content of meat products to match both consumer and health authority demands. The Quick‐Dry‐Slice process (QDS®) technology, in combination with the use of potassium salts as NaCl substitutes, has been successfully used to manufacture salt‐reduced fermented sausages in a short period of time and without added NaCl. Online non‐destructive technologies such as X‐ray and Electromagnetic Induction allow green hams to be classified according to their fat content which is a crucial parameter to adjust the duration of the salting period. X‐ray technologies can also be used to estimate the salt uptake after salting. Information regarding fat and salt contents is important to optimize the dry‐cured ham process by decreasing salt content variability (inter‐ and intra‐ batch) and by reducing the salt content of the final product. Other technologies such as Near Infrared Spectroscopy (NIRS) and Microwave Spectroscopy are useful to control the process and to characterize and classify the product according to its salt content. Most of these technologies can be easily implemented on line in the industry in order to control manufacturing processes, and to produce meat products with the desired characteristics