541 research outputs found
Markov Chain Models of Fecundity in Sheep
10 pages, 1 article*Markov Chain Models of Fecundity in Sheep* (Robson, D. S.; Iniguez, Luis) 10 page
A Lattice Monte Carlo study of inverse symmetry breaking in a two scalar model in three-dimensions.
Continuum limit of finite temperature lambda phi**4 in three-dimensions from lattice Monte Carlo.
Udder measurements and milk production in two Awassi sheep genotypes and their crosses
To improve the effectiveness of community-based breeding programs for increased milk production, the values of different udder measurements for predicting milk production traits during the milking period were assessed over 3 yr on 273 Awassi ewes. Machine milking of ewes began after weaning, 56 d after parturition, and continued until the milk yield of the ewes was < 200 mL/d. Milk yield obtained by hand milking and milk composition were measured weekly, and days in milk, total milk yield, and total yields of protein, fat, and nonfat solids in milk were calculated for each ewe. On d 70 of milking, morphological traits of the whole udder (circumference, width, height, and length), udder cistern (height), and teats (length, width, and position score) were measured. On the same day, the milk yield of ewes was recorded by hand milking. Positive and moderate to strong correlations (r = 0.36 to 0.76) between udder circumference and width, teat width, and milk production traits of total milk yield, and total yields of protein, fat, and nonfat solids were found. However, a more accurate predictor of milk production traits was milk yield on d 70, as higher positive correlations between this variable and the milk production traits were found (r = 0.63 to 0.89). Nine farmers were invited to independently estimate the hand-milked milk yield performance of a sample of 169 ewes (d 15 to 45 of milking) by visually observing each ewe and making a subjective linear score (1 to 5). Their assessments were significantly correlated with milk yield on the day of the observation (r = 0.52), total milk yield (r = 0.50), and days in milk (r = 0.45). Considering the perception details provided by farmers concerning each of the subjective linear scores, it was found that most predictive linear udder measurements of udder circumference and width and teat width identified in this study were implicit in these scores. The predictive ability of the measurements studied have practical implications for community-based breeding programs involving improvement of milk production-not just in Syria, but in other countries in dry areas as well-because it is possible for experienced farmers to visually assess milk production of dairy ewes or take simple udder measurements with predictive value
Adherence to Mediterranean diet reduces the prevalence of obesity and abdominal obesity at 4 years and the risk of incident abdominal obesity at 9 years in children of the INMA study
Annual Scientific Meeting of the European Society for Clinical Investigation “Precision medicine for healthy ageing” (52nd. 2018. Barcelona)L Notario-Barandiaran, MG de la Hera, E Pereda, A Fernandez-Somoano, M Guxens, S Gonzalez-Palacios, D Valera-Gran, L Torres-Collado, LS Marina, A Tardon, M Vrijheid, C Iniguez, J Vioque, EMN Muno
Resistance to Epigenetic-Targeted Therapy Engenders Tumor Cell Vulnerabilities Associated with Enhancer Remodeling
Drug resistance represents a major challenge to achieving durable responses to cancer therapeutics. Resistance mechanisms to epigenetically targeted drugs remain largely unexplored. We used bromodomain and extra-terminal domain (BET) inhibition in neuroblastoma as a prototype to model resistance to chromatin modulatory therapeutics. Genome-scale, pooled lentiviral open reading frame (ORF) and CRISPR knockout rescue screens nominated the phosphatidylinositol 3-kinase (PI3K) pathway as promoting resistance to BET inhibition. Transcriptomic and chromatin profiling of resistant cells revealed that global enhancer remodeling is associated with upregulation of receptor tyrosine kinases (RTKs), activation of PI3K signaling, and vulnerability to RTK/PI3K inhibition. Large-scale combinatorial screening with BET inhibitors identified PI3K inhibitors among the most synergistic upfront combinations. These studies provide a roadmap to elucidate resistance to epigenetic-targeted therapeutics and inform efficacious combination therapies. Using functional screens, profiling of drug-resistant cells, and drug combination screens in neuroblastoma, Iniguez et al. show that PI3K pathway activation via enhancer remodeling and transcriptional reprogramming confers resistance to BET inhibitors (BETi) and that PI3K inhibitors synergize with BETi
SUMOylation of the mitochondrial fission protein Drp1 occurs at multiple nonconsensus sites within the B domain and is linked to its activity cycle
[[abstract]]Dynamin-related protein (Drp) 1 is a key regulator of mitochondrial fission and is composed of GTP-binding, Middle, insert B, and C-terminal GTPase effector (GED) domains. Drp1 associates with mitochondrial fission sites and promotes membrane constriction through its intrinsic GTPase activity. The mechanisms that regulate Drp1 activity remain poorly understood but are likely to involve reversible post-translational modifications, such as conjugation of small ubiquitin-like modifier (SUMO) proteins. Through a detailed analysis, we find that Drp1 interacts with the SUMO-conjugating enzyme Ubc9 via multiple regions and demonstrate that Drp1 is a direct target of SUMO modification by all three SUMO isoforms. While Drp1 does not harbor consensus SUMOylation sequences, our analysis identified2 clusters of lysine residues within the B domain that serve as noncanonical conjugation sites. Although initial analysis indicates that mitochondrial recruitment of ectopically expressed Drp1 in response to staurosporine is unaffected by loss of SUMOylation, we find that Drp1 SUMOylation is enhanced in the context of the K38A mutation. This dominant-negative mutant, which is deficient in GTP binding and hydrolysis, does not associate with mitochondria and prevents normal mitochondrial fission. This finding suggests that SUMOylation of Drp1 is linked to its activity cycle and is influenced by Drp1 localization.-Figueroa-Romero, C., Iniguez-Lluhi, J. A., Stadler, J., Chang, C.-R., Arnoult, D., Keller, P. J., Hong, Y., Blackstone, C., Feldman, E. L. SUMOylation of the mitochondrial fission protein Drp1 occurs at multiple nonconsensus sites within the B domain and is linked to its activity cycle.[[fileno]]2050155010001[[department]]生科
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