Glutathione-S-transferase A3 protein suppresses thiram-induced tibial dyschondroplasia by regulating prostaglandin-related genes expression.

Tibial dyschondroplasia (TD) is an intractable avian cartilage disease in which proximal growth plates of tibia lack blood vessels and contain nonviable cells, and it leads to the inflammatory response. Prostaglandins (PGs) genes have not been studied yet in TD chicken, and they might play role in skeletal metabolism, therefore we planned to explore the role of recombinant glutathione-S-transferase A3 (rGSTA3) protein and PG-related genes. In this study, qRT-PCR, enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) analysis were used to identify the expression patterns of eight PG-related genes in the tibial growth plate of broiler chicken. The results showed that the expression of PG-related genes glutathione-S-transferase A3 (GSTA3), cyclooxygenase 2 (COX-2), prostaglandin D2 synthase (PTGDS), prostaglandin E synthase (PTGES), prostaglandin E2 receptor (PTGER) 3, PTGER4, prostaglandin reductase 1 (PTGR1) and hematopoietic prostaglandin D synthases (HPGDS) expression were identified and could significantly respond to thiram-induced TD chicken. Interestingly, the expression of rate-limiting enzyme COX-2 and PGE2 were induced after the treatment of rGSTA3 protein. These findings demonstrated that the occurrence of TD is closely related to the inhibition of PGs. Moreover, rGSTA3 protein participated in the recovery of TD by strengthening the expression of PG-related genes.

[Clinical, genetic and pathological features of neuronal ceroid lipofuscinosis in 5 Chinese patients].

Objective: To report the clinical, genetic and ultrastructural pathological features of neuronal ceroid lipofuscinosis (NCLs) in 5 Chinese patients. Methods: A total of 5 patients with NCLs were collected from 2013 to 2015 diagnosed by the department of pediatrics of Beijing Tian Tan Hospital. Their clinical, electrophysiological and neuroimaging data of the patients were reviewed.A total of 9 underlying genes of NCLs were tested in 4 cases and their parents.Ultrastructural pathology by skin biopsy was performed in 3 cases respectively. Results: We identified two novel homozygous mutations and one novel heterozygous pathogenic mutation in 3 patients. The confirmed mutations included c. 1153G >C (p.Gly385Arg) MFSD8 homozygous mutation, c 321-1G >A CLN5 intron splice site homozygous mutation and c 407G >A (p.Arg136His)CLN6 heterozygous mutation, which had never been reported before. While no gene mutation was detected in the rest 1 case. Among the 3 cases received electron microscope testing of skin biopsy, 2 presented with fingerprint inclusions mixed with granular osmiophilic deposits, rectilinear profiles mixed with granular osmiophilic deposits were noted in another case. Conclusions: The patients of NCLs caused by the mutations of MFSD8, CLN5 and CLN6 genes in Chinese population were firstly reported in this study. There are some relevence between genotype, pathomorphology and clinical presentation of NCLs. The pathomorphology is still a gold standard for the diagnosis of NCLs.

Iron-embedded C2N monolayer: a promising low-cost and high-activity single-atom catalyst for CO oxidation.

An Fe-embedded C2N monolayer as a promising single-atom catalyst for CO oxidation by O2 has been investigated based on first-principles calculations. It is found that the single Fe atom can be strongly trapped in the cavity of the C2N monolayer with a large adsorption energy of 4.55 eV and a high diffusion barrier of at least 3.00 eV to leave the cavity, indicating that Fe should exist in the isolated single-atom form. Due to the localized metal 3d orbitals near the Fermi level, the embedded Fe single-atom catalyst has a high chemical activity for the adsorption of CO and O2 molecules. CO oxidation by O2 on the catalyst would proceed via a two-step mechanism. The first step of the CO oxidation reaction has been studied via the Langmuir-Hinshelwood and Eley-Rideal mechanisms with energy barriers of 0.46 and 0.65 eV, respectively. The second step of the CO oxidation reaction follows the Eley-Rideal mechanism with a much smaller energy barrier of 0.24 eV. For both the steps, the CO2 molecules produced are weakly adsorbed on the substrates, suggesting that the proposed catalyst will not be poisoned by the generated CO2. Our results indicate that the Fe-embedded C2N monolayer is a promising single-atom catalyst for CO oxidation by O2 at low temperatures.

Effect of alloying additions on the hydrogen-induced grain boundary embrittlement in iron.

Using ab initio density functional theory calculations, we have investigated the influence of Mo, V and Pd on the H-induced grain boundary embrittlement in Fe. We find that, in the high impurity concentration systems, all of the three alloying elements facilitate H embrittlement at the Σ3 (111) [Formula: see text] grain boundary in Fe. The calculated binary effects of the H-X (X = Mo, V, Pd) couples are 0.063, 0.074 and 0.040 eV, respectively. On the other hand, in the large unit cell with low impurity concentration, both Mo and V can facilitate H embrittlement, and the binary effects of pairs are 0.152 and 0.164 eV, respectively. While Pd reduces the H embrittlement on the cohesion of the Fe grain boundary with the binary effect of - 0.1 eV. The H-X (X = Mo, V, Pd) interactions are interpreted by electronic structure analyses.

The CRP-cAMP complex and downregulation of the glnAp2 promoter provides a novel regulatory linkage between carbon metabolism and nitrogen assimilation in Escherichia coli.

In Escherichia coli, glnA (encoding glutamine synthetase) is transcribed from two promoters (glnAp1 and glnAp2). The glnAp1 is a sigma(70)-dependent promoter that is activated by the cAMP receptor protein (CRP). Under nitrogen-deficient growth conditions, glnAp1 is repressed by NtrC-phosphate. The downstream glnAp2 promoter is sigma(54)-dependent and is activated by NtrC-phosphate. Here, we show that glnAp2 expression is affected by different carbon sources and that the CRP-cAMP complex inhibits the glnAp2 promoter activity. Primer extension and KMnO4 footprinting analysis indicate that the inhibitory effect is at the transcriptional level in vivo. When glnAp2 is activated by NifA, a similar inhibitory effect by CRP-cAMP is observed. Site-directed mutagenesis and deletion analysis indicate that the characterized and putative CRP-binding sites located in the upstream region of the glnAp2 promoter are not essential for the inhibitory effect. CRP-cAMP inhibits sigma(54)-dependent glnAp2 strongly, by 21-fold. By activating glnAp1 and downregulating glnAp2, the overall effect of CRP-cAMP on glnA expression is an approximately fourfold reduction, which correlates with the reduction of gamma-glutamyl transferase activities in the cells. We propose therefore that a physiological role of CRP-cAMP activation of glnAp1 is to partially compensate for CRP-cAMP downregulation of glnAp2, allowing a low but non-negligible level of expression of the important genes transcribed from it. A novel regulatory linkage between carbon and nitrogen regulons is proposed.