Integrative Neuroscience Initiative on Alcoholism

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To prevent malaria deathly infections, the Plasmodium circumsporozoite- protein (CSP) have been targeted to develop most recent vaccines inducing anti-CSP antibodies with ~ 70 % protection. In contrast, anti-CSP drug-like small-molecules remain underdeveloped to possible complement such anti-CSP tool-box. Computational predictions mimicking natural co-evolution are described here trying to bypass the tridimensional shield-coat of CSP disordered-repeats. Tens of thousands of raw-children were generated by co-evolution from home-designed molecular parents. Hundreds of CSP fitted-children predicting low molecular weights, hydrophilicities, toxicities and nanoMolar affinities, were identified. Some of the resulting non-toxic fitted-children either cross-docked the CSP signal peptide and C-terminal α-helices and/or targeted other ordered CSP cavities. These repeat-independent drug-like anti-CSP evolved-ligand predictions, provide some proof-of-concept examples for basic in vitro experimentation.

BackgroundInbreeding depression can adversely affect traits related to fitness, reproduction and productive performance. Although current research suggests that inbreeding levels are generally low in most goat breeds, the impact of inbreeding depression on phenotypes of economic interest has only been investigated in a few studies based on genealogical data.ResultsWe genotyped 1040 goats with the Goat SNP50 BeadChip. This information was used to estimate different molecular inbreeding coefficients and characterise runs of homozygosity and homozygosity patterns. We detected 38 genomic regions with increased homozygosity as well as 8 ROH hotspots mapping to chromosomes 1, 2, 4, 6, 14, 16 and 17. Eight hundred seventeen goats with available records for dairy traits were analysed to evaluate the potential consequences of inbreeding depression on milk phenotypes. Four regions on chromosomes 8 and 25 were significantly associated with inbreeding depression for the natural logarithm of the somatic cell count. Notably, these regions contain several genes related with immunity, such as SYK, IL27, CCL19 and CCL21. Moreover, one region on chromosome 2 was significantly associated with inbreeding depression for milk yield.ConclusionsAlthough genomic inbreeding levels are low in Murciano-Granadina goats, significant evidence of inbreeding depression for the logarithm of the somatic cell count, a phenotype closely associated with udder health and milk yield, have been detected in this population. Minimising inbreeding would be expected to augment economic gain by increasing milk yield and reducing the incidence of mastitis, which is one of the main causes of dairy goat culling.

La nature et la distribution des phénotypes quantitatifs représentent une connaissance de base pour l’application des méthodologies génétiques dans les plans de sélection des animaux domestiques. Afin d’illustrer l’action de facteurs non génétiques d’aridité sur la distribution phénotypique des performances individuelles de la croissance des chevreaux de la population locale élevés dans des conditions restrictives et irrégulières, 945 chevreaux issus de 285 chèvres et 19 boucs, nés durant la période 1998–2014, ont été étudiés par l’analyse des distributions des poids jusqu’à 150 jours d’âge. La dispersion des poids représentait une expression collective des génotypes des chevreaux dans les conditions de l’étude avec des variations dues à la fois aux effets génétiques et environnementaux. L’hypothèse de la normalité n’a été vérifiée qu’aux âges de 10 jours et 30 jours quand les chevreaux étaient surtout nourris sous la mère et n’étaient pas directement dépendants des ressources alimentaires du parcours aride. Durant une année défavorable, les performances enregistrées ont suivi une distribution particulière expliquée par le fait que les chevreaux performants ont été incapables d’extérioriser leur supériorité. Par conséquent, le milieu aride a réduit les performances de la population caprine locale. En outre, il a limité l’expression de quelques génotypes fortement productifs. Cette spécificité de l’action du milieu aride incite à un approfondissement indispensable pour ajuster les méthodes de sélection aux conditions des milieux restrictifs et des groupes génétiques adaptés.

Abstract Background: Phenotypic variability for productive and meat quality traits has been largely studied in Iberian pigs, especially in genetic selection and nutritional experiments. Complex interactions among genetic background, diet composition and gut microbiota difficult the evaluation of true effects of each factor on phenotypes. In order to disentangle these interactions, we evaluated changes in gut microbiota composition comparing Iberian and Duroc pigs fed diets with different energy source.Results: Gut microbiota composition was analysed in feces from 48 pigs (Iberian and Duroc) fed a standard diet or a sunflower oil-enriched diet with high oleic acid content (6%). A higher richness was observed for Iberian pigs (p < 0.05) and compositional analysis was applied for beta-diversity, differential abundance and pairwise log-ratio analyses. We found significant differences in overall microbiota composition between breeds, and also between diets inside breeds, to a lesser extent. Differential abundance analysis revealed that Duroc animals have more proportion of Actinobacteria and Prevotella, while Iberian replace those microorganisms with other more variable taxa. According to dietary differences, high-oleic fed animals were richer in Prevotella. We also found microbial ratios capable of separating animals by breeds and diets, mostly related to Actinobacteria.Conclusion: This study reveals that both genetic background and diet composition might have a relevant impact in gut microbiota composition. The application of compositional data analysis has facilitated the identification of microorganisms and ratios as possibly related to metabolic changes due to genetic background and, to a lower extent, to dietary changes. This may lead to a relevant progress in the knowledge of interactions between pig genetics, environment and gut microbiota.

Simple SummaryPlants in the Opuntia genus are abundant and can be used as a feed supplement because they are highly digestible and can provide water and energy. We fed sheep during late gestation with alfalfa (Control), Opuntia (Opuntia) or protein-enriched Opuntia (E-Opuntia) and measured milk yield and postnatal growth in the progeny. Birth weight did not differ among treatments (p > 0.05) but progeny from E-Opuntia grew faster (p < 0.01) and were heavier at weaning (p < 0.05), despite the fact that Control ewes produced more milk (p < 0.05). Feeding ewes with Opuntia (protein enriched or not) during the last third of gestation is an option for reducing production costs in underfed females managed under extensive conditions in arid and semiarid regions.The present study tested whether feeding ewes during the last third of pregnancy with cladodes of Opuntia (untreated or protein-enriched), as an alternative to alfalfa hay, would improve milk yield as well as the pre- and post-natal growth of their lambs. Sixty mature Rambouillet ewes and their progeny were randomly allocated among three nutritional treatments: (i) Control, fed alfalfa; (ii) Opuntia, fed untreated cladodes; (iii) E-Opuntia, fed protein-enriched cladodes (pre-treated with urea and ammonium sulphate). Birth weight did not differ among treatments (p > 0.05) but Control ewes produced more milk than both groups of Opuntia-fed ewes (p < 0.05). However, milk yield was not related to the growth of the progeny (p > 0.05) because lambs from E-Opuntia-fed ewes grew faster (p < 0.01) and were heavier at weaning (p < 0.05) than lambs from the other two groups. We conclude that Opuntia (with or without protein enrichment) can be used as an alternative to alfalfa hay for feeding ewes during the last third of pregnancy and therefore reduce production costs under extensive conditions in arid and semiarid regions. Moreover, protein-enriched Opuntia appears to improve postnatal lamb growth.

Preimplantation embryos experience profound resetting of epigenetic information inherited from the gametes. Genome-wide analysis at single-base resolution has shown similarities but also species differences between human and mouse preimplantation embryos in DNA methylation patterns and reprogramming. Here, we have extended such analysis to two key livestock species, the pig and the cow. We generated genome-wide DNA methylation and whole-transcriptome datasets from gametes to blastocysts in both species. In oocytes from both species, a distinctive bimodal methylation landscape is present, with hypermethylated domains prevalent over hypomethylated domains, similar to human, while in the mouse the proportions are reversed.An oocyte-like pattern of methylation persists in the cleavage stages, albeit with some reduction in methylation level, persisting to blastocysts in cow, while pig blastocysts have a highly hypomethylated landscape. In the pig, there was evidence of transient de novo methylation at the 8–16 cell stages of domains unmethylated in oocytes, revealing a complex dynamic of methylation reprogramming. The methylation datasets were used to identify germline differentially methylated regions (gDMRs) of known imprinted genes and for the basis of detection of novel imprinted loci. Strikingly in the pig, we detected a consistent reduction in gDMR methylation at the 8–16 cell stages, followed by recovery to the blastocyst stage, suggesting an active period of imprint stabilization in preimplantation embryos. Transcriptome analysis revealed absence of expression in oocytes of both species of ZFP57, a key factor in the mouse for gDMR methylation maintenance, but presence of the alternative imprint regulator ZNF445. In conclusion, our study reveals species differences in DNA methylation reprogramming and suggests that porcine or bovine models may be closer to human in key aspects than in the mouse model.

espanolSe realizaron dos ensayos para evaluar el efecto de dietas con diferentes niveles de factores antinutritivos: inhibidores de tripsina y quimotripsina (UTI, UQI respectivamente, como unidades) de guisantes de invierno y γGlutamyl-S-Ethenyl-Cysteine de alberjon, en el rendimiento de lechones durante el perio - do estarter. En cada uno se utilizaron 192 machos castrados, hibridos Duroc x (Large-White x Landrace), con 11,23 y 11,55 kg de peso medio respectivamente, e igual diseno: cuatro tratamientos y ocho replicas cada una de seis lechones. Los tratamientos del Ensayo 1 fueron: Control: harina de soja 47 y soja ex - trusionada (0,97 UTI-1,94 UQI/mg de pienso); P-CAR: soja extrusionada y guisante Cartouche (1,62 UTI3,16 UQI/mg de pienso); P-ICE: soja extrusionada y guisante Iceberg (3,09 UTI-4,95 UQI/mg de pienso); P-LUN: soja extrusionada y guisante Luna (3,19 UTI-5,56 UQI/mg de pienso). Los lechones del tratamiento P-CAR crecieron significativamente mas que el resto, con igual consumo y conversion. No hubo diferencias entre Control, P-ICE y P-LUN. El pienso del Ensayo 2 incluia diferentes niveles de alberjon: 0%, 5%, 15% y 25%, y en consecuencia de γGlutamyl-S-Ethenyl-Cysteine (1,52% del grano). Los lechones del tratamiento 5% comieron y crecieron mas, con igual conversion que los del tratamiento 0%. El rendimiento empeoro con porcentajes del 15% o mayores. Se concluye que lechones de 40 a 61 dias de vida mantienen o mejoran el rendimiento con la ingesta de inhibidores de proteasas que exceden 3,28 y 2,86 veces, UTI y UQI respectivamente, los de una dieta de soja, y que la inclusion de 5% de alberjon en el pienso aumenta el consumo y el crecimiento EnglishTwo trials were conducted to evaluate the effect of diets with different levels of anti-nutritional factors: trypsin (TIU) and chymotrypsin (CIU) inhibitors units of peas and γGlutamyl-S-Ethenyl-Cysteine (GEC) of narbon vetch, in productive performance of pigs from 40 to 61 days of age. 192 barrows were used in each test, Duroc hybrid x (Large White x Landrace), with 11.23 and 11.55 kg body weight respectively, and the same experimental design: four treatments and eight replicates with six piglets in each case. In trial 1 treatments were: Control: soybean meal 47 and soybean extruded (0.97 TIU-1.94 CIU/mg feed); P-CAR: soybean extruded and pea Cartouche (1.62 TIU-3.16 CIU/mg feed); P-ICE: soybean extruded and pea Iceberg (3.09 TIU-4.95 CIU/mg feed); P-LUN: soybean extruded and pea Luna (3.19 TIU-5.56 CIU/mg feed). The piglets of P-CAR treatment grew significantly faster than the others, with the same intake and feed conversion. No significant differences between Control, P-ICE and P-LUN. In trial 2 the feedstuff had different levels of narbon vetch: 0%, 5%, 15% and 25%, and consequently of γGlutamyl-S-Ethenyl-Cysteine (1.52% of the grain). The piglets that consumed the treatment of 5% had higher intake and growth, and the same conversion that piglets feeding with the treatment of 0%. The performance worsened significantly with increasing 15%. We conclude that piglets in starter period maintain or improve the performance with intake of proteases inhibitors in feedstuff that exceed 3.28 (TIU) and 2.86 (CIU) times those of a control diet, and that the inclusion of 5% of narbon vetch in feedstuff increases feed intake and growth

The aim of this study was to determine the effect of the parity on productive performance (lactation length, total milk yield and milk yield by day of calving interval) and calving interval in water buffaloes. For this purpose, records of 663 lactations from 248 buffaloes were evaluated. Total milk yield was 1344.91 liters, lactation length was 291.20 days, calving interval was 453.55 days and milk by day of calving was 2.77 liters. Parity did not significantly affect total milk yield, but had a significant effect on lactation length, calving interval and milk by day of calving interval. First calving buffaloes had a longer lactation, a longer calving interval and in consequence lower productivity than buffaloes with two and three or more calving. Second calving buffaloes had intermediate and significantly different values than buffaloes with three or more calving. Calving interval was positively correlated with total milk yield (r = 0.34983, p &lt;0.0001) and length of lactation (r = 0.67408, p = &lt;0.0001); and negatively with milk by day of calving (r = -0.41263, p&lt;0.0001). In conclusion, parity affected the productive performance and calving interval, with buffaloes of one and two calving being less productive due to a longer calving interval. An increase of milk yield is related with a longer calving interval, therefore, buffaloes of one and two calving, must be provided with optimal management conditions, which allow them to support milk yield and not to compromise the reproductive performance