Suppression of cell cycle progression by Jun dimerization protein (JDP2) involves down-regulation of cyclin A2

We report here a novel role for Jun dimerization protein-2 (JDP2) as a regulator of the progression of normal cells through the cell cycle. To determine the role of JDP2 in vivo, we generated Jdp2 knock-out (Jdp2KO) mice by targeting exon 1 to disrupt the site of initiation of transcription. The healing of wounded skin of Jdp2KO mice proceeded more rapidly than that of control mice and more proliferating cells were found at wound margins. Fibroblasts derived from embryos of Jdp2KO mice proliferated more rapidly and formed more colonies than wild-type fibroblasts. JDP2 was recruited to the promoter of the gene for cyclin A2 (ccna2) at a previously unidentified AP-1 site. Cells lacking Jdp2 had elevated levels of cyclin A2 mRNA. Moreover, reintroduction of JDP2 resulted in repression of transcription of ccna2 and of cell cycle progression. Thus, transcription of the gene for cyclin A2 appears to be a direct target of JDP2 in the suppression of cell proliferation

Spontaneous breaking and re-making of the RS-Au-SR staple in self-assembled ethylthiolate/Au(111) interface

The stability of the self-assembled RS–Au–SR (R = CH₂CH₃)/Au­(111) interface at room temperature has been investigated using scanning tunneling microscopy (STM) in conjunction with density functional theory (DFT) and MD calculations. The RS–Au–SR staple, also known as Au-adatom-dithiolate, assembles into staple rows along the [112̅] direction. STM imaging reveals that while the staple rows are able to maintain a static global structure, individual staples within the row are subjected to constant breaking and remaking of the Au–SR bond. The C₂S–Au–SC₂/Au­(111) interface is under a dynamic equilibrium and it is far from rigid. DFT/MD calculations show that a transient RS–Au–Au–SR complex can be formed when a free Au atom is added to the RS–Au–SR staple. The relatively high reactivity of the RS–Au–SR staple at room temperature could explain the reactivity of thiolate-protected Au nanoclusters, such as their ability to participate in ligand exchange and intercluster reactions

Overexpressed transferrin receptor implied poor prognosis and relapse in gastrointestinal stromal tumors

Ferroptosis, as a novel-induced programmed cell death, plays critical roles in the pathogenesis of cancers. However, the promising biomarkers of ferroptosis in gastrointestinal stromal tumor (GIST) remain to be elucidated. Herein, the expression of ferroptosis-related genes was analyzed in GIST. Among the 64 ferroptosis-related genes, transferrin receptor (TFRC) expression presented a remarkable upregulation in high-risk patients through Gene Expression Omnibus (GEO) dataset analysis, as well as its significant change after imatinib was treated. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of TFRC-relevant genes revealed that TFRC expression was closely associated with cell growth pathways and metabolism-related pathways. Furthermore, patients at high risk of recurrence were more likely to exhibit high TFRC expression by immunohistochemistry. Additionally, high TFRC expression indicated an undesirable state of patient relapse, which could serve as a powerful significant independent predictor of recurrence-free survival (RFS). In summary, we systematically summarize the expression characteristics and clinical relevance of TFRC and show that TFRC can be used as a prognostic factor, which can be considered a potential therapeutic target in GIST

A Tradeoff Drives the Evolution of Reduced Metal Resistance in Natural Populations of Yeast

Various types of genetic modification and selective forces have been implicated in the process of adaptation to novel or adverse environments. However, the underlying molecular mechanisms are not well understood in most natural populations. Here we report that a set of yeast strains collected from Evolution Canyon (EC), Israel, exhibit an extremely high tolerance to the heavy metal cadmium. We found that cadmium resistance is primarily caused by an enhanced function of a metal efflux pump, PCA1. Molecular analyses demonstrate that this enhancement can be largely attributed to mutations in the promoter sequence, while mutations in the coding region have a minor effect. Reconstruction experiments show that three single nucleotide substitutions in the PCA1 promoter quantitatively increase its activity and thus enhance the cells' cadmium resistance. Comparison among different yeast species shows that the critical nucleotides found in EC strains are conserved and functionally important for cadmium resistance in other species, suggesting that they represent an ancestral type. However, these nucleotides had diverged in most Saccharomyces cerevisiae populations, which gave cells growth advantages under conditions where cadmium is low or absent. Our results provide a rare example of a selective sweep in yeast populations driven by a tradeoff in metal resistance

Stimulation of ZPC Production by Follicle-Stimulating Hormone in the Granulosa Cells of Japanese Quail (Coturnix Japonica)

Avian perivitelline membrane, an investment homologous to the zona pellucida of mammalian oocytes, is composed of two glycoproteins. Previous studies have indicated that one of the components, a glycoprotein homologous to mammalian ZPC, is produced and secreted by the granulosa cells of maturing follicles in quail ovary. In the present study, to investigate the hormonal regulation of ZPC production, [3H] leucine incorporation into ZPC was compared in granulosa cells cultured in a medium containing follicle-stimulating hormone (FSH), luteinizing hormone, or prolactin, and a stimulatory effect of FSH was observed. By measuring ZPC protein in the medium and mRNA in the cells with Western blotting and Northern blotting analyses, respectively, we found that addition of FSH stimulated not only ZPC protein production but also ZPC mRNA expression in the granulosa cells. These results suggested that FSH stimulates ZPC protein production at the gene transcription level

Evaluation and Analysis of Traditional Physical Training by Using Mobile Edge Computing and Software-Defined Networking

The body health plays an important metric in people’s everyday life, and it directly determines whether people have the ability to preferably contribute to the society. In fact, the physical training is a universal sport to enhance the body health. Therefore, the evaluation and analysis of physical training become particularly significant. With the rapid development and emerging of new techniques and networking paradigms, the traditional offline physical training evaluation and analysis cannot be performed well. Instead, this paper uses Mobile Edge Computing (MEC) and Software-Defined Networking (SDN) to implement the evaluation and analysis of physical training, shortened for MSPT, where MEC is the new computing technique and SDN is the new networking paradigm. The proposed MSPT includes two parts. At first, the physical training data from different mobile devices are migrated into the edge server for computing according to the current condition, in which the game theory is used to complete the task scheduling. Then, SDN is responsible for the global scheduling in the centralized control manner, in which the multigranularity scheduling strategy is used to handle the traffic between the SDN controller and edge computing server. The experiments are driven by OMNet, including three aspects of evaluation, i.e., task offloading of MEC, traffic scheduling of SDN, and performance analysis of physical training, and the results show that the proposed MSPT has better performance than the corresponding baselines

Nonlinear behaviour of damaged concrete bridge structures under moving vehicular loads

Recently, there has been increased interest in using non-linear vibration techniques to detect damage in concrete bridge structures. It is necessary to understand the nonlinear behavior of concrete structures under vibration loading for damage detection. In this paper, a damage beam element is developed to analyse the non-linear dynamic behaviour of damaged concrete bridge structures subject to moving vehicular loads. The damage is modelled as a combination of a rotational spring and shear effect due to the concrete cracking and local bond deterioration of the concrete-steel interface. Numerical simulations are presented to study the damage effects on the dynamic behaviour of concrete bridge structures under moving vehicular loads. The results show that the model is reliable and effective to describe the damage in the concrete bridge structures