To avoid zinc (Zn) toxicity, plants have developed a Zn homeostasis mechanism to cope with Zn excess in the surrounding soil. In this report, we uncovered the difference of a cross-homeostasis system between iron (Fe) and Zn in dealing with Zn excess in the Zn hyperaccumulator Arabidopsis halleri ssp. gemmifera and nonhyperaccumulator Arabidopsis thaliana. Arabidopsis halleri shows low expression of the Fe acquisition and deficiency response-related genes IRT1 and IRT2 compared with A. thaliana. In A. thaliana, lowering the expression of IRT1 and IRT2 through the addition of excess Fe to the medium increases Zn tolerance. Excess Zn induces significant Fe deficiency in A. thaliana and reduces Fe accumulation in shoots. By contrast, the accumulation of Fe in shoots of A. halleri was stable under various Zn treatments. Root ferric chelate reductase (FRO) activity and expression of FIT are low in A. halleri compared with A. thaliana. Overexpressing a ZIP family member IRT3 in irt1-1, rescues the Fe-deficient phenotype. A fine-tuned Fe homeostasis mechanism in A. halleri maintains optimum Fe level by Zn-regulated ZIP transporters and prevents high Zn uptake through Fe-regulated metal transporters, and in part be responsible for Zn tolerance
Spider silk is protein fibers with extraordinary mechanical properties. Up to now, it is still poorly understood how silk proteins are kept in a soluble form before spinning into fibers and how the protein molecules are aligned orderly to form fibers. Minor ampullate spidroin is one of the seven types of silk proteins, which consists of four types of domains: N-terminal domain, C-terminal domain (CTD), repetitive domain (RP) and linker domain (LK). Here we report the tertiary structure of CTD and secondary structures of RP and LK in aqueous solution, and their roles in protein stability, solubility and fiber formation. The stability and solubility of individual domains are dramatically different and can be explained by their distinct structures. For the tri-domain miniature fibroin, RP-LK-CTDMi, the three domains have no or weak interactions with one another at low protein concentrations (<1 mg/ml). The CTD in RP-LK-CTDMi is very stable and soluble, but it cannot stabilize the entire protein against chemical and thermal denaturation while it can keep the entire tri-domain in a highly water-soluble state. In the presence of shear force, protein aggregation is greatly accelerated and the aggregation rate is determined by the stability of folded domains and solubility of the disordered domains. Only the tri-domain RP-LK-CTDMi could form silk-like fibers, indicating that all three domains play distinct roles in fiber formation: LK as a nucleation site for assembly of protein molecules, RP for assistance of the assembly and CTD for regulating alignment of the assembled molecules.
Prostate transmembrane protein androgen induced 1 (PMEPA1) has been reported to promote cancer progression. Metastasis is the main factor leading to cancer progression and poor prognosis, and at the beginning of metastasis, epithelial‐to‐mesenchymal transition (EMT) is a crucial activation. However, the relationship between PMEPA1 and EMT in colorectal cancer metastasis is still poorly understood. In this study, we first testified that PMEPA1 expresses higher in tumour than normal tissue in Gene Expression Omnibus database, in the Cancer Genome Atlas (TCGA) as well as in the clinical data we collected. Moreover, the higher expression was associated with poor prognosis. We furthermore demonstrated PMEPA1 promotes colorectal cancer metastasis and EMT in vivo and in vitro. We found that PMEPA1 activates the bone morphogenetic proteins (BMP) signalling of TGF‐β signalling resulting in promoting EMT and accelerating the proliferation and metastasis of colorectal cancer.
Abstract:Objective: Three mainstream techniques-laparoscopic hepatectomy (LH), percutaneous radiofrequency ablation (pRFA), and open hepatectomy (OH)-were compared in this study, in terms of their efficacies in the treatment of small hepatocellular carcinoma (HCC). Methods: A comparative study was performed within a total of 94 patients diagnosed with small HCC in our hospital from 2005 to 2010, who underwent LH (28), RFA (33), or OH (33). They had either a single tumor lesion of less than 5 cm or up to three nodules with diameters of less than 3 cm each. Outcomes were carefully evaluated throughout a 3-year follow-up interval and statistically interpreted. Results: The pRFA group had a significantly lower disease-free survival rate compared with the two surgical groups (P=0.001) and significantly shorter overall survival (P=0.005), while the LH group and the OH group had no difference in survival results. For patients younger than 60 years old, surgical approaches offered a better long-term overall survival prognosis (P=0.008). There were no statistically significant differences among the three groups in overall survival for elderly patients (P=0.104). Conclusions: Among patients with small HCC, LH may provide better curative effects than pRFA without increasing complication rates. pRFA leads to faster recurrence than surgical resections. LH has similar therapeutic effects to OH and causes less trauma. For patients younger than 60 years old, LH may be the best curative treatment. Elderly patients may choose either surgery or pRFA.
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