Body condition alters glutathione and nuclear factor erythroid 2-like 2 (NFE2L2)-related antioxidant network abundance in subcutaneous adipose tissue of periparturient Holstein cows

[EN] Dairy cows with high body condition score (BCS) in late prepartum are more susceptible to oxidative stress (OS). Nuclear factor erythroid 2-like 2 (NFE2L2) is a major antioxidant transcription factor. We investigated the effect of precalving BCS on blood biomarkers associated with OS, inflammation, and liver function, along with mRNA and protein abundance of targets related to NFE2L2 and glutathione (GSH) metabolism in s.c. adipose tissue (SAT) of periparturient dairy cows. Twenty-two multiparous Holstein cows were retrospectively classified into a high BCS (HBCS; n = 11, BCS ¿3.5) or normal BCS (NBCS; n = 11, BCS ¿3.17) on d 28 before parturition. Cows were fed a corn silage- and wheat straw-based total mixed ration during late prepartum, and a corn silage- and alfalfa hay-based total mixed ration postpartum. Blood samples obtained at ¿10, 7, 15, and 30 d relative to parturition were used for analyses of biomarkers associated with inflammation, including albumin, ceruloplasmin, haptoglobin, and myeloperoxidase, as well as OS, including ferric reducing ability of plasma (FRAP), reactive oxygen species (ROS), and ß-carotene. Adipose biopsies harvested at ¿15, 7, and 30 d relative to parturition were analyzed for mRNA (real-time quantitative PCR) and protein abundance (Western blotting) of targets associated with the antioxidant transcription regulator nuclear factor, NFE2L2, and GSH metabolism pathway. In addition, concentrations of GSH, ROS and malondialdehyde were measured. High BCS cows had lower prepartum dry matter intake expressed as a percentage of body weight along with greater BCS loss between ¿4 and 4 wk relative to parturition. Plasma concentrations of ROS and FRAP increased after parturition regardless of treatment. Compared with NBCS, HBCS cows had greater concentrations of FRAP at d 7 postpartum, which coincided with peak values in those cows. In addition, NBCS cows experienced a marked decrease in plasma ROS after d 7 postpartum, while HBCS cows maintained a constant concentration by d 30 postpartum. Overall, ROS concentrations in SAT were greater in HBCS cows. However, overall mRNA abundance of NFE2L2 was lower and cullin 3 (CUL3), a negative regulator of NFE2L2, was greater in HBCS cows. Although HBCS cows had greater overall total protein abundance of NFE2L2 in SAT, ratio of phosphorylated NFE2L2 to total NFE2L2 was lower, suggesting a decrease in the activity of this antioxidant system. Overall, mRNA abundance of the GSH metabolism-related genes glutathione reductase (GSR), glutathione peroxidase 1 (GPX1), and transaldolase 1 (TALDO1), along with protein abundance of glutathione S-transferase mu 1 (GSTM1), were greater in HBCS cows. Data suggest that HBCS cows might experience greater systemic OS after parturition, while increased abundance of mRNA and protein components of the GSH metabolism pathway in SAT might help alleviate tissue oxidant status. Data underscored the importance of antioxidant mechanisms at the tissue level. Thus, targeting these pathways in SAT during the periparturient period via nutrition might help control tissue remodeling while allowing optimal performance.Y. Liang is a recipient of a doctoral fellowship from China Scholarship Council (CSC, Beijing, China). A. S. Alharthi received a fellowship from King Saud University to perform his PhD studies at the University of Illinois (Urbana). A. A. Elolimy was recipient of a fellowship from Higher Education Ministry, Egypt to perform his Ph.D. studies at the University of Illinois (Urbana). We thank Perdue AgriBusiness (Salisbury, MD) for the donation of ProvAAL2 AADvantage during the course of the experiment. 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Measurement of the (90,91,92,93,94,96)Zr(n,gamma) and (139)La(n,gamma) cross sections at n_TOF

Open AccessNeutron capture cross sections of Zr and La isotopes have important implications in the field of nuclear astrophysics as well as in the nuclear technology. In particular the Zr isotopes play a key role for the determination of the neutron density in the He burning zone of the Red Giant star, while the (139)La is important to monitor the s-process abundances from Ba up to Ph. Zr is also largely used as structural materials of traditional and advanced nuclear reactors. The nuclear resonance parameters and the cross section of (90,91,92,93,94,96)Zr and (139)La have been measured at the n_TOF facility at CERN. Based on these data the capture resonance strength and the Maxwellian-averaged cross section were calculated

No association between polymorphisms/haplotypes of the vascular endothelial growth factor gene and preeclampsia

<p>Abstract</p> <p>Background</p> <p>Preeclampsia (PE) is the first worldwide cause of death in pregnant women, intra-uterine growth retardation, and fetal prematurity. Some vascular endothelial grown factor gene (<it>VEGF</it>) polymorphisms have been associated to PE and other pregnancy disturbances. We evaluated the associations between <it>VEGF </it>genotypes/haplotypes and PE in Mexican women.</p> <p>Methods</p> <p>164 pregnant women were enrolled in a case-control study (78 cases and 86 normotensive pregnant controls). The rs699947 (-2578C/A), rs1570360 (-1154G/A), rs2010963 (+405G/C), and rs25648 (-7C/T), <it>VEGF </it>variants were discriminated using Polymerase Chain Reaction - Restriction Fragment Length Polymorphism (PCR-RFLP) methods or Taqman single nucleotide polymorphism (SNP) assays.</p> <p>Results</p> <p>The proportions of the minor allele for rs699947, rs1570360, rs2010963, and rs25648 <it>VEGF </it>SNPs were 0.33, 0.2, 0.39, and 0.17 in controls, and 0.39, 0.23, 0.41, and 0.15 in cases, respectively (<it>P </it>values > 0.05). The most frequent haplotypes of rs699947, rs1570360, rs2010963, and rs25648 <it>VEGF </it>SNPs, were C-G-C-C and C-G-G-C with frequencies of 0.39, 0.21 in cases and 0.37, 0.25 in controls, respectively (<it>P </it>values > 0.05)</p> <p>Conclusion</p> <p>There was no evidence of an association between <it>VEGF </it>alleles, genotypes, or haplotypes frequencies and PE in our study.</p

Phosphoproteomic analysis of neoadjuvant breast cancer suggests that increased sensitivity to paclitaxel is driven by CDK4 and filamin A

Precision oncology research is challenging outside the contexts of oncogenic addiction and/or targeted therapies. We previously showed that phosphoproteomics is a powerful approach to reveal patient subsets of interest characterized by the activity of a few kinases where the underlying genomics is complex. Here, we conduct a phosphoproteomic screening of samples from HER2-negative female breast cancer receiving neoadjuvant paclitaxel (N = 130), aiming to find candidate biomarkers of paclitaxel sensitivity. Filtering 11 candidate biomarkers through 2 independent patient sets (N= 218) allowed the identification of a subgroup of patients characterized by high levels of CDK4 and filamin-A who had a 90% chance of achieving a pCR in response to paclitaxel. Mechanistically, CDK4 regulates filamin-A transcription, which in turn forms a complex with tubulin and CLIP-170, which elicits increased binding of paclitaxel to microtubules, microtubule acetylation and stabilization, and mitotic catastrophe. Thus, phosphoproteomics allows the identification of explainable factors for predicting response to paclitaxel

New measurement of neutron capture resonances of 209Bi

The neutron capture cross section of Bi209 has been measured at the CERN n TOF facility by employing the pulse-height-weighting technique. Improvements over previous measurements are mainly because of an optimized detection system, which led to a practically negligible neutron sensitivity. Additional experimental sources of systematic error, such as the electronic threshold in the detectors, summing of gamma-rays, internal electron conversion, and the isomeric state in bismuth, have been taken into account. Gamma-ray absorption effects inside the sample have been corrected by employing a nonpolynomial weighting function. Because Bi209 is the last stable isotope in the reaction path of the stellar s-process, the Maxwellian averaged capture cross section is important for the recycling of the reaction flow by alpha-decays. In the relevant stellar range of thermal energies between kT=5 and 8 keV our new capture rate is about 16% higher than the presently accepted value used for nucleosynthesis calculations. At this low temperature an important part of the heavy Pb-Bi isotopes are supposed to be synthesized by the s-process in the He shells of low mass, thermally pulsing asymptotic giant branch stars. With the improved set of cross sections we obtain an s-process fraction of 19(3)% of the solar bismuth abundance, resulting in an r-process residual of 81(3)%. The present (n,gamma) cross-section measurement is also of relevance for the design of accelerator driven systems based on a liquid metal Pb/Bi spallation target.Comment: 10 pages, 5figures, recently published in Phys. Rev.