In this study, we identified the ZmCLA4 gene, which is responsible for the qLA4-1 associated with leaf angle, by positional cloning, and parsed the genetic mechanism.
Summary
The purpose of this study was to investigate the effects of long‐term treatment with dexamethasone (DEX) on the antioxidation and nutrition metabolism in broiler chickens. Broilers were ...placed on a high‐nutrient diet for 41 days, and half were given orally DEX‐supplemented water at 20 mg/L every other day from 19 to 41 days of age. DEX treatment downregulated superoxide dismutase activity as well as the mRNA expression of CuZn‐superoxide dismutase and glutathione peroxidase with a decrease in GSH/GSSG ratio and an increase in malondialdehyde level in the liver of broilers. DEX treatment aggravated oxidative damage in the liver and, therefore, increased the sensitivity of broilers to ascites syndrome with higher mortality and reduced growth performance. Serum metabolomics analysis showed that DEX treatment significantly increased the levels of glucose, intermediates in protein metabolism (valine, proline, serine, threonine and urea) and lipid metabolism‐related products (palmitic acid, stearic acid and cholesterol) while decreasing the levels of β‐hydroxy butyric acid, succinic acid and malic acid, demonstrating that DEX treatment inhibited the Krebs cycle and the oxidation of fatty acids, and promoted the de novo synthesis of fatty acids as well as protein decomposition in the liver of broilers. Additionally, detection of metabolism‐related enzymes revealed that DEX treatment inhibited glycolysis and promoted glycogen decomposition. In summary, DEX treatment resulted in oxidative stress and glucose and lipid metabolism disorders in the broilers.
Methionine aminopeptidases (MetAPs), which remove methionine residue from newly synthesized polypeptide chains, are a class of metalloproteases ubiquitously distributed in both eukaryotes and ...prokaryotes. MetAP-2 inhibition can induce G1 cell cycle arrest, cytostasis in tumor cells in vitro and inhibition of tumor growth in vivo. The discovery of fumagillin with potent antiangiogenic and antiproliferative activities promoted the development of fumagillin analogues as a novel class of anticancer agents. Early drug discovery efforts have focused on analogs of fumagillin, which irreversibly inhibit MetAP-2 through covalent modification of an epoxide. Several fumagillin analogs, like CKD-732, TNP-470 and PPI-2458, were found to be potent selective inhibitors of MetAP-2 (proteolytic activity) and endothelial cell proliferation. Further, they have entered in clinical trials for the treatment of different types of tumors. Recently, attention has been paid to reversible human MetAP-2 inhibitors, such as bengamides, 2-hydroxy-3-aminoamides, anthranilic acid sulfonamides and triazole analogs, which have demonstrated their potential to inhibit angiogenesis and tumor growth in vivo as well. This review article mainly discussed the development of MetAP-2 inhibitors in cancer therapy and also summarized their structure-activity relationships.
In humans, obesity is associated with increased or decreased levels of serum biochemical indicators. However, the relationship is not as well understood in chickens. Due to long-term intense ...selection for fast growth rate, modern broilers have the problem of excessive fat deposition, exhibiting biochemical or metabolic changes. In the current study, the Northeast Agricultural University broiler lines divergently selected for abdominal fat content (NEAUHLF) were used to identify differences in serum biochemical parameters between the 2 lines. A total of 18 serum biochemical indicators were investigated in the 16th, 17th, and 18th generation populations of NEAUHLF, and the genetic parameters of these serum biochemical indicators were estimated. After analyzing the data from these 3 generations together, the results showed that the levels of 16 of the tested serum biochemical parameters were significantly different between the lean and fat birds. In the fat birds, serum concentrations of high-density lipoprotein cholesterol (HDL-C), HDL-C:low-density lipoprotein cholesterol (LDL-C), total bile acid, total protein, albumin, globulin, aspartate transaminase (AST):alanine transaminase (ALT), γ-glutamyl transpeptidase (GGT), uric acid, and creatinine were very significantly higher (P < 0.01), whereas LDL-C, albumin:globulin, glucose, AST, ALT, and free fatty acids concentrations in serum were very significantly lower than those in the lean birds (P < 0.01). Of these 16 serum biochemical parameters, 5 (LDL-C, HDL-C:LDL-C, total bile acid, albumin, and albumin:globulin) had high heritabilities (0.58 ≤ h2 ≤ 0.89), 6 (HDL-C, total protein, globulin, AST:ALT, GGT, and creatinine) had moderate heritabilities (0.29 ≤ h2 ≤ 0.48), and the remaining 5 had low heritabilities (h2 < 0.20). Serum HDL-C, HDL-C:LDL-C, and glucose had higher positive genetic correlation coefficients (rg) with abdominal fat traits (0.30 ≤ rg ≤ 0.80), whereas serum globulin, AST, and uric acid showed higher negative genetic correlations with abdominal fat traits (–0.62 ≤ rg ≤ –0.30). The remaining 10 serum biochemical parameters had lower genetic correlations with abdominal fat traits (–0.30 < rg < 0.30). In conclusion, we identified serum HDL-C and HDL-C:LDL-C levels as potential biomarkers for selection of lean birds. These findings will also be useful in future studies for investigating obesity and lipid metabolism in humans as well as in other animal species.
KEY MESSAGE : Stripe rust resistance transferred from Thinopyrum intermedium into common wheat was controlled by a single dominant gene, which mapped to chromosome 1B near Yr26 and was designated ...YrL693. Stripe rust caused by Puccinia striiformis f. sp. tritici (Pst) is a highly destructive disease of wheat (Triticum aestivum). Stripe rust resistance was transferred from Thinopyrum intermedium to common wheat, and the resulting introgression line (L693) exhibited all-stage resistance to the widely virulent and predominant Chinese pathotypes CYR32 and CYR33 and to the new virulent pathotype V26. There was no cytological evidence that L693 had alien chromosomal segments from Th. intermedium. Genetic analysis of stripe rust resistance was performed by crossing L693 with the susceptible line L661. F₁, F₂, and F₂:₃ populations from reciprocal crosses showed that resistance was controlled by a single dominant gene. A total 479 F₂:₃ lines and 781 pairs of genomic simple sequence repeat (SSR) primers were employed to determine the chromosomal location of the resistance gene. The gene was linked to six publicly available and three recently developed wheat genomic SSR markers. The linked markers were localized to wheat chromosome 1B using Chinese Spring nulli-tetrasomic lines, and the resistance gene was localized to chromosome 1B based on SSR and wheat genomic information. A high-density genetic map was also produced. The pedigree, molecular marker data, and resistance response indicated that the stripe rust resistance gene in L693 is a novel gene, which was temporarily designated YrL693. The SSR markers that co-segregate with this gene (Xbarc187-1B, Xbarc187-1B-1, Xgwm18-1B, and Xgwm11-1B) have potential application in marker-assisted breeding of wheat, and YrL693 will be useful for broadening the genetic basis of stripe rust resistance in wheat.
It is unclear how quiescence is enforced in naive T cells, but activation by foreign antigens and self-antigens is allowed, despite the presence of inhibitory signals. We showed that active ...transforming growth factor β (TGF-β) signaling was present in naive T cells, and T cell receptor (TCR) engagement reduced TGF-β signaling during T cell activation by downregulating TGF-β type 1 receptor (TβRI) through activation of caspase recruitment domain-containing protein 11 (CARD11) and nuclear factor κB (NF-κB). TGF-β prevented TCR-mediated TβRI downregulation, but this was abrogated by interleukin-6 (IL-6). Mitigation of TCR-mediated TβRI downregulation through overexpression of TβRI in naive and activated T cells rendered T cells less responsive and suppressed autoimmunity. Naive T cells in autoimmune patients exhibited reduced TβRI expression and increased TCR-driven proliferation compared to healthy subjects. Thus, TCR-mediated regulation of TβRI-TGF-β signaling acts as a crucial criterion to determine T cell quiescence and activation.
Display omitted
•Naive T cells show active TGF-β signaling and TβR expression•Strong TCR stimulation decreases TβRI and TGF-β signaling by CARD11 and NF-κB•Overexpression of TβRI suppresses T cell response and autoimmunity•TβRI expression is reduced in naive T cells of SLE patients
It is unclear how quiescence is enforced in naive T cells, yet activation is allowed. Tu et al. show that TGF-β signaling maintains T cell quiescence. Strong TCR stimuli reduce TβRI expression and consequently abolish TGF-β signaling in T cells. TCR-mediated TβRI downregulation acts as a “third criterion” to fully activate T cells in addition to the “two-signal” model.
Summary
What is known and objective
A series of studies have indicated that valproic acid (VPA) plasma concentration decreased rapidly when used concomitantly with carbapenem antibiotics, including ...meropenem (MEPM), imipenem and panipenem, which may increase the risk of seizure breakthrough. However, the cause for the change in VPA pharmacokinetics is unclear. A retrospective analysis of VPA therapeutic drug monitoring (TDM) records was performed to investigate this VPA pharmacokinetics drug–drug interaction.
Methods
Three hundred and eighty one VPA TDM records from the Department of Neurosurgery of Xiangya Hospital from January 2012 to December 2014 were collected. The VPA TDM records were categorized by VPA and MEPM daily dosages in grams/day (g/day). A comparison of VPA plasma levels among different groups was performed to investigate the change in VPA level in this drug interaction.
Results and discussion
Remarkable decreases in VPA plasma level were observed when the drug was used concomitantly with MEPM in both 1.2 g/d and 1.6 g/d VPA groups (67·3 ± 4·6 μg/mL, n = 21 vs. 15·3 ± 1·9 μg/mL, n = 15, P < 0·001; 67·6 ± 1·2 μg/mL vs. 18·1 ± 2·6 μg/mL, n = 38, P < 0·001). No significant difference in VPA plasma concentrations was observed between the 1·2 g/day VPA + MEPM, 1·6 g/day VPA + MEPM and 2·0 g/day VPA + MEPM groups (15·3 ± 1·9 μg/mL, n = 15 vs. 18·1 ± 2·6 μg/mL, n = 38 vs. 9·0 ± 3·0 μg/mL, n = 7; P = 0·252). The decrease in VPA concentration was independent of MEPM daily dose (14·0 ± 5·1 μg/mL, n = 4 for high MEPM daily dose vs. 16·5 ± 1·9 μg/mL, n = 56 for low MEPM daily dose; P = 0·729). After discontinuation of MEPM for more than 7 days, VPA plasma concentration recovered to a value comparable to that before MPEM initiation (69·7 ± 4·2 μg/mL, n = 21 vs. 51·2 ± 8·1 μg/mL, n = 9; P = 0·48).
What is new and conclusion
This is the first study using a large number of VPA TDM records to investigate the change in VPA levels caused by concomitant use of MEPM. Our results imply that the decrease in drug concentration cannot be reversed by increasing VPA dose. Moreover, MEPM daily dose did not influence the drop in VPA plasma level. At least 7 days are required for the recovery of VPA plasma concentration after discontinuation of MEPM.
The magnitude of decrease in VPA plasma concentration was independent of VPA and MEPM daily dose in this drug‐drug interaction.
Performance of the BL03U beamline at SSRF Sun, Z. P.; Liu, Z. H.; Liu, Z. T. ...
Journal of synchrotron radiation,
September 2020, Letnik:
27, Številka:
5
Journal Article
Recenzirano
The vacuum ultraviolet beamline BL03U with a photon energy range from 7 eV upwards has been constructed at the 3.5 GeV Shanghai Synchrotron Radiation Facility. Equipped with an APPLE‐Knot undulator, ...this beamline is dedicated to angle‐resolved photoemission spectroscopy. An energy‐resolving power of higher than 4.6 × 104 has been achieved in the photon energy range 21.6–48 eV, which is almost the same as the theoretical estimation.
The design and performance test of the vacuum ultraviolet beamline BL03U at SSRF are described.
Microstructural evolution of the as-forged Ti-44Al-8Nb-0.2W-0.2B-Y alloy during high temperature tensile tests between 650 and 950°C, at strain rates of 1×10−4s−1, 2×10−4s−1 and 5×10−4s−1, is ...investigated in this study. Tensile properties of the alloy are extremely sensitive to the test temperature and strain rate. At a strain rate of 5×10−4s−1, ductile-brittle transition temperature (DBTT) of this alloy is between 750 and 800°C. At lower temperatures, the principal deformation mechanism involves breaking down of remnant lamellar structure and deformation of twins. Above 900°C, dynamic recrystallization (DRX) occurs and the extent of DRX improves with an increase in temperature and strain as well as a decrease in strain rate. Under specific test conditions, the ω phase forms by the solid-state phase transformation: α2→γ+ω. The inhomogeneous microstructure remarkably influences the mechanical properties of the hot-forged pancake.
PDF
