Abscisic acid (ABA) plays an essential role in seed germination. In this study, we demonstrate that one SNF1-RELATED PROTEIN KINASE3-type protein kinase, SOS2-LIKE PROTEIN KINASE5 (PKS5), is involved in ABA signal transduction via the phosphorylation of an interacting protein, ABSCISIC ACID-INSENSITIVE5 (ABI5). We found that pks5-3 and pks5-4, two previously identified PKS5 superactive kinase mutants with point mutations in the PKS5 FISL/NAF (a conserved peptide that is necessary for interaction with SOS3 or SOS3-LIKE CALCIUM BINDING PROTEINs) motif and the kinase domain, respectively, are hypersensitive to ABA during seed germination. PKS5 was found to interact with ABI5 in yeast (Saccharomyces cerevisiae), and this interaction was further confirmed in planta using bimolecular fluorescence complementation. Genetic studies revealed that ABI5 is epistatic to PKS5. PKS5 phosphorylates a serine (Ser) residue at position 42 in ABI5 and regulates ABA-responsive gene expression. This phosphorylation was induced by ABA in vivo and transactivated ABI5. Expression of ABI5, in which Ser-42 was mutated to alanine, could not fully rescue the ABA-insensitive phenotypes of the abi5-8 and pks5-4abi5-8 mutants. In contrast, mutating Ser-42 to aspartate rescued the ABA insensitivity of these mutants. These data demonstrate that PKS5-mediated phosphorylation of ABI5 at Ser-42 is critical for the ABA regulation of seed germination and gene expression in Arabidopsis (Arabidopsis thaliana).

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β-amyloid 1-42 (Aβ1-42)-induced learning and memory impairment in rats is believed to be associated with inflammation. Cytokine production is a key pathologic event in the progression of inflammatory processes. In this rat study, soybean isoflavones (SIF) was used to investigate it's protective effects on inflammation caused by β-amyloid 1-42 (Aβ1-42), which is associated with learning and memory impairment in Alzheimer disease. We characterized the learning and memory ability. cytokine profiles of circulating interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) in the serum and the expression of Toll like receptor4 (TLR4) and nuclear factor-κB p65 (NF-κB p65) mRNA and protein in the brain tissue following intracerebroventricular administration of Aβ1-42 by miniosmotic pump for 14 days. The results showed that functional deficits of learning and memory in SIF treatment groups were significantly improved compared to the control group without SIF treatment in water maze test. The serum IL-1β and TNF-α level were significantly increased, and the expressions of TLR4 and NF-κB p65 mRNA and protein in the brain were up-regulated, indicating inflammation response was initiated following administration of Aβ1-42. After intragastric pre-treatment with SIF, inflammatory cytokines was significantly reduced and also SIF reversed the Aβ1-42 induced up-regulation of TLR4 and NF-κB p65 mRNA and protein expression in the brain and expression of NF-κB p65 in nuclei. These results suggested that SIF reduced the cytokine cascade and inflammatory response induced by Aβ1-42 which could result in the improvement of spatial learning and memory ability impairment in the rats.

Gastric cancer is a prevalent tumor that is usually detected at an advanced metastatic stage. Currently, standard therapies are mostly ineffective. Here, we report that Glypican-3 (GPC3) is absent in invasive tumors and metastatic lymph nodes, in particular in aggressive and highly disseminated signet ring cell carcinomas. We demonstrate that loss of GPC3 correlates with poor overall survival in patients. Moreover, we show that absence of GPC3 causes up-regulation of MAPK/FoxM1 signaling and that blockade of this pathway alters cellular invasion. An inverse correlation between GPC3 and FoxM1 is also shown in patient samples. These data identify GPC3 as a potential metastasis suppressor gene and suggest its value as a prognostic marker in gastric cancer. Development of therapies targeting signaling downstream of GPC3 are warranted.

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The use of cardiopulmonary bypass (CPB) in cardiac surgeries is known to induce pathological changes in vital organs such as lungs. Remote ischemic preconditioning (RIPC) is a protective strategy that has shown to be able to reduce tissue damage related to ischemia-reperfusion injury (IRI). The current study seeks to evaluate the beneficial effects of limb RIPC on lung tissues and function in a rat CPB model. RIPC, which consisted of three cycles of 5-min ischemia and subsequently 5-min reperfusion, was induced in the hind limbs of the animals via a tourniquet. Bronchoalveolar lavage (BAL) fluid analysis and hematoxylin and eosin staining revealed that limb RIPC could significantly attenuate CPB-induced pulmonary injury, as evidenced by a combination of lower total BAL protein content, less severe alveolar wall thickening and reduced intra-alveolar neutrophil infiltration. Consistently, RIPC was also found to improve the proliferation capacity of the bronchioalveolar stem cells isolated from the lung tissues in rats subjected to surgical procedure with CPB. These beneficial effects translated into significantly improved lung function. Further investigation suggested that RIPC could up-regulate the serum levels of several anti-inflammatory cytokines such as interleukin (IL)-4 and 10, which might play a role in its pulmonoprotective effects. Taken together, the current study provided convincing evidence that limb RIPC could be a useful strategy for minimizing CPB-induced organ injuries in patients undergoing CPB surgery.

bZIP (basic leucine zipper) transcription factors coordinate plant growth and development and control responses to environmental stimuli. The genome of Chinese cabbage (Brassica rapa) encodes 136 putative bZIP transcription factors. The bZIP transcription factors in Brassica rapa (BrbZIP) are classified into 10 subfamilies. Phylogenetic relationship analysis reveals that subfamily A consists of 23 BrbZIPs. Two BrbZIPs within subfamily A, Bra005287 and Bra017251, display high similarity to ABI5 (ABA Insensitive 5). Expression of subfamily A BrbZIPs, like BrABI5a (Bra005287/BrbZIP14) and BrABI5b (Bra017251/BrbZIP13), are significantly induced by the plant hormone ABA. Subcellular localization assay reveal that both BrABI5a and BrABI5b have a nuclear localization. BrABI5a and BrABI5b could directly stimulate ABA Responsive Element-driven HIS (a HIS3 reporter gene, which confers His prototrophy) or LUC (LUCIFERASE) expression in yeast and Arabidopsis protoplast. Deletion of the bZIP motif abolished BrABI5a and BrABI5b transcriptional activity. The ABA insensitive phenotype of Arabidopsis abi5-1 is completely suppressed in transgenic lines expressing BrABI5a or BrABI5b. Overall, these results suggest that ABI5 orthologs, BrABI5a and BrABI5b, have key roles in ABA signalling in Chinese cabbage.