To plants, copper is vitally essential at low concentrations but extremely toxic at elevated concentrations. Plants have evolved a suite of mechanisms that modulate the uptake, distribution, and utilization of copper ions. These mechanisms require copper-interacting proteins for transporting, chelating, and sequestrating copper ions. In this study, we have systematically screened for copper-interacting proteins in Arabidopsis roots via copper-immobilized metal affinity chromatography (Cu-IMAC). We also compared Arabidopsis root metalloproteomes with affinity to Cu-IMAC and Zn-IMAC. From the identities of 38 protein spots with affinity to Cu-IMAC, 35 unique proteins were identified. Functional classification of these proteins includes redox/hydrolytic reactions, amino acid metabolism, glutathione metabolism, phosphorylation, translation machinery, membrane-associated proteins, and vegetative storage proteins. Potential copper-interacting motifs were predicted and scored. Six candidate motifs, H-(X)5 -H, H-(X)7 -H, H-(X)12 -H, H-(X)6 -M, M-(X)7 -H, and H-(X)3 -C, are present in Cu-IMAC-isolated proteins with higher frequency than in the whole Arabidopsis proteome.

No abstract

No abstract

Rationale: Endometriosis is a highly prevalent gynecological disease in women of reproductive age that markedly reduces life quality and fertility. Unfortunately, there is no cure for this disease, which highlights that more efforts are needed to investigate the underlying mechanism for designing novel therapeutic regimens. This study aims to investigate druggable membrane receptors distinctively expressed in endometriotic cells. Methods: Bioinformatic analysis of public databases was employed to identify potential druggable candidates. Normal endometrial tissues and ectopic endometriotic lesions were obtained for the determination of target genes. Primary endometrial and endometriotic stromal cells as well as two different mouse models of endometriosis were used to characterize molecular mechanisms and therapeutic outcomes of endometriosis, respectively. Results: Anthrax toxin receptor 2 (ANTXR2) mRNA and protein are upregulated in the endometriotic specimens. Elevation of ANTXR2 promotes endometriotic cell adhesion, proliferation, and angiogenesis. Furthermore, hypoxia is the driving force for ANTXR2 upregulation via altering histone modification of ANTXR2 promoter by reducing the repressive mark, histone H3 lysine 27 (H3K27) trimethylation, and increasing the active mark, H3K4 trimethylation. Activation of ANTXR2 signaling leads to increased Yes-associated protein 1 (YAP1) nuclear translocation and transcriptional activity, which contributes to numerous pathological processes of endometriosis. Pharmacological blocking of ANTXR2 signaling not only prevents endometriotic lesion development but also causes the regression of established lesion. Conclusion: Taken together, we have identified a novel target that contributes to the disease pathogenesis of endometriosis and provided a potential therapeutic regimen to treat it.

Objective: Aging is associated with decline in executive function that may lead to reduced dual-task performance. Regular exercise has been recommended for promoting or maintaining mental and physical health in older adults, yet only a fraction of older adults exercise regularly. Exergame training may have the potential to enhance exercise adherence. Therefore, the aim of this study was to examine the effects of exergame-based dual-task training on executive function and dual-task performance in community-dwelling older adults. Materials and Methods: This was a single-blinded, randomized-controlled trial. Twenty community-dwelling older adults were recruited and randomly assigned to one of two groups. All participants completed 36 trainings, including three 60-minute sessions/week over 12 weeks. Participants in the experimental group received exergame-based dual-task training, while those in the control group received home-based multicomponent exercise training. Measures of executive function, dual-task performance, and community walking ability were assessed before and after the intervention. Results: Significant group • time interactions (P = 0.000-0.027) with large effects were found in all selected outcome measures. Compared with the control group, the experimental group improved significantly in measures of general executive function (P = 0.014), inhibitory control (P = 0.037), cognitive dual-task performance (P < 0.001), and community walking ability (P = 0.002). Enhanced general executive function was highly correlated with either improved motor dual-task performance (r = 0.674) or improved cognitive dual-task performance (r = -0.701). Conclusion: These results suggested that exergame-based dual-task training improved both executive function and dual-task performance in older people. These positive effects could be transferred to enhance community walking ability. Clinical Trial Registration number: ACTRN 12617000095369.