GSK3 phosphorylates and regulates the Green Revolution protein Rht-B1b to reduce plant height in wheat.

The utilization of stabilized DELLA proteins Rht-B1b and Rht-D1b was crucial for increasing wheat (Triticum aestivum) productivity during the Green Revolution. However, the underlying mechanisms remain to be clarified. Here, we cloned a gain-of-function allele of the GSK3/SHAGGY-like kinase-encoding gene GSK3 by characterizing a dwarf wheat mutant. Furthermore, we determined that GSK3 interacts with and phosphorylates the Green Revolution protein Rht-B1b to promote it to reduce plant height in wheat. Specifically, phosphorylation by GSK3 may enhance the activity and stability of Rht-B1b, allowing it to inhibit the activities of its target transcription factors. Taken together, we reveal a positive regulatory mechanism for the Green Revolution protein Rht-B1b by GSK3, which might have contributed to the Green Revolution in wheat.

Q negatively regulates wheat salt tolerance through directly repressing the expression of TaSOS1 and reactive oxygen species scavenging genes.

The Q transcription factor plays important roles in improving multiple wheat domestication traits such as spike architecture, threshability and rachis fragility. However, whether and how it regulates abiotic stress adaptation remain unclear. We found that the transcriptional expression of Q can be induced by NaCl and abscisic acid treatments. Using the q mutants generated by CRISPR/Cas9 and Q overexpression transgenic lines, we showed that the domesticated Q gene causes a penalty in wheat salt tolerance. Then, we demonstrated that Q directly represses the transcription of TaSOS1-3B and reactive oxygen species (ROS) scavenging genes to regulate Na+ and ROS homeostasis in wheat. Furthermore, we showed that wheat salt tolerance protein TaWD40 interacts with Q to competitively interfere with the interaction between Q and the transcriptional co-repressor TaTPL. Taken together, our findings reveal that Q directly represses the expression of TaSOS1 and some ROS scavenging genes, thus causing a harmful effect on wheat salt tolerance.

Sequential activation of strigolactone and salicylate biosynthesis promotes leaf senescence.

Leaf senescence is a complex process strictly regulated by various external and endogenous factors. However, the key signaling pathway mediating leaf senescence remains unknown. Here, we show that Arabidopsis SPX1/2 negatively regulate leaf senescence genetically downstream of the strigolactone (SL) pathway. We demonstrate that the SL receptor AtD14 and MAX2 mediate the age-dependent degradation of SPX1/2. Intriguingly, we uncover an age-dependent accumulation of SLs in leaves via transcriptional activation of SL biosynthetic genes by the transcription factors (TFs) SPL9/15. Furthermore, we reveal that SPX1/2 interact with the WRKY75 subclade TFs to inhibit their DNA-binding ability and thus repress transcriptional activation of salicylic acid (SA) biosynthetic gene SA Induction-Deficient 2, gating the age-dependent SA accumulation in leaves at the leaf senescence onset stage. Collectively, our new findings reveal a signaling pathway mediating sequential activation of SL and salicylate biosynthesis for the onset of leaf senescence in Arabidopsis.

Plant-specific BLISTER interacts with kinase BIN2 and BRASSINAZOLE RESISTANT1 during skotomorphogenesis.

Brassinosteroids play an essential role in promoting skotomorphogenesis, yet the underlying mechanisms remain unknown. Here we report that a plant-specific BLISTER (BLI) protein functions as a positive regulator of both BR signaling and skotomorphogenesis in Arabidopsis (Arabidopsis thaliana). We found that the glycogen synthase kinase 3 (GSK3)-like kinase BRASSINOSTEROID INSENSITIVE2 interacts with and phosphorylates BLI at 4 phosphorylation sites (Ser70, Ser146, Thr256, and Ser267) for degradation; in turn, BR inhibits degradation of BLI. Specifically, BLI cooperates with the BRASSINAZOLE RESISTANT1 (BZR1) transcription factor to facilitate the transcriptional activation of BR-responsive genes. Genetic analyses indicated that BLI is essentially required for BZR1-mediated hypocotyl elongation in the dark. Intriguingly, we reveal that BLI and BZR1 orchestrate the transcriptional expression of gibberellin (GA) biosynthetic genes to promote the production of bioactive GAs. Our results demonstrate that BLI acts as an essential regulator of Arabidopsis skotomorphogenesis by promoting BR signaling and GA biosynthesis.

PKL is stabilized by MMS21 to negatively regulate Arabidopsis drought tolerance through directly repressing AFL1 transcription.

Drought stress causes substantial losses in crop production per year worldwide, threatening global food security. Identification of the genetic components underlying drought tolerance in plants is of great importance. In this study, we report that loss-of-function of the chromatin-remodeling factor PICKLE (PKL), which is involved in repression of transcription, enhances drought tolerance of Arabidopsis. At first, we find that PKL interacts with ABI5 to regulate seed germination, but PKL regulates drought tolerance independently of ABI5. Then, we find that PKL is necessary for repressing the drought-tolerant gene AFL1, which is responsible for the drought-tolerant phenotype of pkl mutant. Genetic complementation tests demonstrate that the Chromo domain and ATPase domain but not the PHD domain are required for the function of PKL in regulating drought tolerance. Interestingly, we find that the DNA-binding domain (DBD) is essential for the protein stability of PKL. Furthermore, we demonstrate that the SUMO E3 ligase MMS21 interacts with and enhances the protein stability of PKL. Genetic interaction analysis shows that MMS21 and PKL additively regulate plant drought tolerance. Collectively, our findings uncover a MMS21-PKL-AFL1 module in regulating plant drought tolerance and offer insights into a novel strategy to improve crop drought tolerance.

Mediating effect of subclinical inflammation on the process of morning hypertension leading to atrial fibrillation in community-based older adults.

BACKGROUND: The impacts and mechanisms of morning hypertension (MHT) on the risk of new-onset atrial fibrillation (AF) in the elderly have not been clarified. We aimed to investigate an association between MHT and new-onset AF and explore a mediating effect of subclinical inflammation on this association. METHODS: From 2008 to 2010, 1789 older adults aged ≥60 years were recruited in Shandong area, China. Morning blood pressure (BP) was assessed using 24-hour ambulatory BP monitoring. MHT was defined as BP ≥ 135/85 mm Hg during the period from wake time to 0900 a.m. Subclinical inflammation was assessed by hypersensitive C-reactive protein (hsCRP), tumor necrosis factor-alpha (TNF-α), systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and galectin-3. New-onset AF was rated during the follow-up period. RESULTS: Over an average 129.0 [standard deviation (SD): 21.58] months of follow-up, the hazard ratio of new-onset AF in MHT patients was 1.39 (95% confidence interval: 1.01 to 1.91) compared with non-MHT participants (Padjusted = 0.027). The risk of new-onset AF was 1.17-fold with one-SD increment of morning systolic BP. Subclinical inflammation was significantly associated with new-onset AF. The hazard ratios of new-onset AF were 2.29, 2.04, 2.08, 2.08, 2.03, and 3.25 for one-SD increment in hsCRP, TNF-α, SII, NLR, PLR, and galectin-3, respectively (Padjusted < 0.001). The analysis showed that hsCRP, TNF-α, SII, NLR, PLR, and galectin-3 separately mediated the process of MHT inducing new-onset AF (Padjusted < 0.05). CONCLUSIONS: MHT is associated with an increased risk of new-onset AF. The subclinical inflammation might play a mediating role in this association.

Role of Extracellular Vesicles in Placental Inflammation and Local Immune Balance.

BACKGROUND: Pregnancy maintenance depends on the formation of normal placentas accompanied by trophoblast invasion and vascular remodeling. Various types of cells, such as trophoblasts, endothelial cells, immune cells, mesenchymal stem cells (MSCs), and adipocytes, mediate cell-to-cell interactions through soluble factors to maintain normal placental development. Extracellular vesicles (EVs) are diverse nanosized to microsized membrane-bound particles released from various cells. EVs contain tens to thousands of different RNA, proteins, small molecules, DNA fragments, and bioactive lipids. EV-derived microRNAs (miRNAs) and proteins regulate inflammation and trophoblast invasion in the placental microenvironment. Maternal-fetal communication through EV can regulate the key signaling pathways involved in pregnancy maintenance, from implantation to immune regulation. Therefore, EVs and the encapsulating factors play important roles in pregnancy, some of which might be potential biomarkers. CONCLUSION: In this review, we have summarized published studies about the EVs in the placentation and pregnancy-related diseases. By summarizing the role of EVs and their delivering active molecules in pregnancy-related diseases, it provides novel insight into the diagnosis and treatment of diseases.

A Review of Microwave Thermography Nondestructive Testing and Evaluation.

Microwave thermography (MWT) has many advantages including strong penetrability, selective heating, volumetric heating, significant energy savings, uniform heating, and good thermal efficiency. MWT has received growing interest due to its potential to overcome some of the limitations of microwave nondestructive testing (NDT) and thermal NDT. Moreover, during the last few decades MWT has attracted growing interest in materials assessment. In this paper, a comprehensive review of MWT techniques for materials evaluation is conducted based on a detailed literature survey. First, the basic principles of MWT are described. Different types of MWT, including microwave pulsed thermography, microwave step thermography, microwave pulsed phase thermography, and microwave lock-in thermography are defined and introduced. Then, MWT case studies are discussed. Next, comparisons with other thermography and NDT methods are conducted. Finally, the trends in MWT research are outlined, including new theoretical studies, simulations and modelling, signal processing algorithms, internal properties characterization, automatic separation and inspection systems. This work provides a summary of MWT, which can be utilized for material failures prevention and quality control.

CsMLO8/11 are required for full susceptibility of cucumber stem to powdery mildew and interact with CsCRK2 and CsRbohD.

Powdery mildew (PM) is one of the most destructive diseases that threaten cucumber production globally. Efficient breeding of novel PM-resistant cultivars will require a robust understanding of the molecular mechanisms of cucumber resistance against PM. Using a genome-wide association study, we detected a locus significantly correlated with PM resistance in cucumber stem, pm-s5.1. A 1449-bp insertion in the CsMLO8 coding region at the pm-s5.1 locus resulted in enhanced stem PM resistance. Knockout mutants of CsMLO8 and CsMLO11 generated by CRISPR/Cas9 both showed improved PM resistance in the stem, hypocotyl, and leaves, and the double mutant mlo8mlo11 displayed even stronger resistance. We found that reactive oxygen species (ROS) accumulation was higher in the stem of these mutants. Protein interaction assays suggested that CsMLO8 and CsMLO11 could physically interact with CsRbohD and CsCRK2, respectively. Further, we showed that CsMLO8 and CsCRK2 competitively interact with the C-terminus of CsRbohD to affect CsCRK2-CsRbohD module-mediated ROS production during PM defense. These findings provide new insights into the understanding of CsMLO proteins during PM defense responses.

BIN2 phosphorylates the Thr280 of CO to restrict its function in promoting Arabidopsis flowering.

CONSTANS (CO) is a central regulator of floral initiation in response to photoperiod. In this study, we show that the GSK3 kinase BIN2 physically interacts with CO and the gain-of-function mutant bin2-1 displays late flowering phenotype through down-regulation of FT transcription. Genetic analyses show that BIN2 genetically acts upstream of CO in regulating flowering time. Further, we illustrate that BIN2 phosphorylates the Thr280 residue of CO. Importantly, the BIN2 phosphorylation of Thr280 residue restricts the function of CO in promoting flowering through affecting its DNA-binding activity. Moreover, we reveal that the N-terminal part of CO harboring the B-Box domain mediates the interaction of both CO-CO and BIN2-CO. We find that BIN2 inhibits the formation of CO dimer/oligomer. Taken together, this study reveals that BIN2 regulates flowering time through phosphorylating the Thr280 of CO and inhibiting the CO-CO interaction in Arabidopsis.

Excessive dietary sodium intake augments long-term risk of atrial fibrillation in older adults with hyperglycemia: A community-based prospective cohort study.

AIM: Studies investigating the association between sodium intake and new-onset atrial fibrillation (AF) have come to controversial results. This study aimed to assess the effect of excessive sodium intake on new-onset AF in individuals with hyperglycemia. METHODS: Between April 2007 and November 2011, 2841 community-dwelling individuals aged 60 years and older were recruited from the Shandong area, China. Dietary sodium intake was estimated using 24-hour urine collection within seven consecutive days. Fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c) were assessed. New-onset AF was diagnosed using ICD-10 with codes I48 (I48.0 - I48.9) during follow-up. RESULTS: The findings were that excessive sodium intake significantly and independently increased the risk of new-onset AF in older adults with hyperglycemia: hazard ratio (HR) 1.525 [95% confidence interval 1.147;2.029] adjusted P = 0.004. The risk of new-onset AF increased by 29.3% (HR 1.293 [1.108;1.509] adjusted P = 0.001) with a one-standard deviation increase in sodium intake. Excessive sodium intake synergistically interacted with hyperglycemia on the increased risk of new-onset AF (HR 1.599 [1.342;1.905] adjusted P < 0.001 for FPG and HR 1.516 [1.271;1.808] adjusted P < 0.001 for HbA1c). CONCLUSION: Our findings indicate that excessive sodium intake independently enhances the risk of new-onset AF among patients with hyperglycemia. A sodium-restricted diet may perhaps result in a multiplier effect on reducing the risk of new-onset AF.

TaBZR1 enhances wheat salt tolerance via promoting ABA biosynthesis and ROS scavenging.

Brassinosteroids (BRs) are vital plant steroid hormones involved in numerous aspects of plant life including growth, development, and responses to various stresses. However, the underlying mechanisms of how BR regulates abiotic stress responses in wheat (Triticum aestivum L.) remain to be elucidated. Here, we find that BR signal core transcription factor BRASSINAZOLE-RESISTANT1 (TaBZR1) is significantly up-regulated by salt treatment. Overexpression of Tabzr1-1D (a gain-of-function TaBZR1 mutant protein) improves wheat salt tolerance. Furthermore, we show that TaBZR1 binds directly to the G-box motif in the promoter of ABA biosynthesis gene TaNCED3 to activate its expression and promotes ABA accumulation. Moreover, TaBZR1 associates with the promoters of ROS-scavenging genes TaGPX2 and TaGPX3 to activate their expression. Taken together, our results elucidate that TaBZR1 improves salt-stress tolerance by activating some genes involved in the biosynthesis of ABA and ROS scavenging in wheat, which gives us a new strategy to improve the salt tolerance of wheat.

[Regulation of crop agronomic traits and abiotic stress responses by brassinosteroids: a review].

Plant adaptation to adverse environment depends on transmitting the external stress signals into internal signaling pathways, and thus forming a variety of stress response mechanisms during evolution. Brassinosteroids (BRs) is a steroid hormone and widely involved in plant growth, development and stress response. BR is perceived by cell surface receptors, including the receptor brassinosteroid-insensitive 1 (BRI1) and the co-receptor BRI1-associated-kinase 1 (BAK1), which in turn trigger a signaling cascade that leads to the inhibition of BIN2 and activation of BES1/BZR1 transcription factors. BES1/BZR1 can directly regulate the expression of thousands of downstream responsive genes. Studies in the model plant Arabidopsis thaliana have shown that members of BR biosynthesis and signal transduction pathways, particularly protein kinase BIN2 and its downstream transcription factors BES1/BZR1, can be extensively regulated by a variety of environmental factors. In this paper, we summarize recent progresses on how BR biosynthesis and signal transduction are regulated by complex environmental factors, as well as how BR and environmental factors co-regulate crop agronomic traits, cold and salt stress responses.

Wheat male-sterile 2 reduces ROS levels to inhibit anther development by deactivating ROS modulator 1.

Ms2 is an important dominant male-sterile gene in wheat, but the biochemical function of Ms2 and the mechanism by which it causes male sterility remain elusive. Here, we report the molecular basis underlying Ms2-induced male sterility in wheat. We found that activated Ms2 specifically reduces the reactive oxygen species (ROS) signals in anthers and thereby induces termination of wheat anther development at an early stage. Furthermore, our results indicate that Ms2 is localized in mitochondria, where it physically interacts with a wheat homolog of ROS modulator 1 (TaRomo1). Romo1 positively regulates the ROS levels in humans but has never been studied in plants. We found that single amino acid substitutions in the Ms2 protein that rescue the ms2 male-sterile phenotype abolish the interaction between Ms2 and TaRomo1. Significantly, Ms2 promotes the transition of TaRomo1 proteins from active monomers to inactive oligomers. Taken together, our findings unravel the molecular basis of Ms2-induced male sterility and reveal a regulatory mechanism in which ROS act as essential signals guiding the anther development program in wheat.

MIR156-Targeted SPL9 Is Phosphorylated by SnRK2s and Interacts With ABI5 to Enhance ABA Responses in Arabidopsis.

The miR156-targeted SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) transcription factors play key roles in regulating plant development, but little is known about their function in abscisic acid (ABA) signaling. Here, we report that the miR156-targeted SPLs enhance ABA responses and contribute to the inhibition of pre-harvest sprouting. We find that SPL9 directly activates the expression of ABA responsive genes through binding to their promoters. SPL9 was further shown to physically interact with ABSCISIC ACID INSENSITIVE 5 (ABI5), a master transcription factor in ABA signaling, thus promoting its association with the promoters of ABA responsive genes. Furthermore, we reveal that the protein kinases SnRK2s interact with and phosphorylate SPL9, which is essential for its role in the activation of ABA responses. Together, our results disclose a SnRK2s-SPLs-ABI5 regulatory module in ABA signaling in Arabidopsis.

Simultaneous analysis of anthocyanins and flavonols in petals of lotus (Nelumbo) cultivars by high-performance liquid chromatography-photodiode array detection/electrospray ionization mass spectrometry.

A fast and reliable HPLC method for the simultaneous separation of anthocyanins and flavonols in lotus petals was developed based on the study of four candidate solvent systems. Fifteen flavonoids were identified by high-performance liquid chromatography with photodiode array detection/mass spectrometry. Among them, two anthocyanins and nine flavonols were discovered in lotus petals for the first time. This work is valuable for both the hybrid breeding on lotus oriented to flower color and the utilization of lotus petals as functional food materials.

Cell type-dependent bimodal p53 activation engenders a dynamic mechanism of chemoresistance.

Studies of drug resistance mostly characterize genetic mutation, and we know much less about phenotypic mechanisms of drug resistance, especially at a quantitative level. p53 is an important mediator of cellular response to chemotherapy, but even p53 wild-type cells vary in drug sensitivity for unclear reasons. Here, we elucidated a new resistance mechanism to a DNA-damaging chemotherapeutic through bimodal modulation of p53 activation dynamics. By combining single-cell imaging with computational modeling, we characterized a four-component regulatory module, which generates bimodal p53 dynamics through coupled feed-forward and feedback, and found that the inhibitory strength between ATM and Mdm2 determined the differential modular output between drug-sensitive and drug-resistant cancer cell lines. We further showed that the combinatorial inhibition of Mdm2 and Wip1 was an effective strategy to alter p53 dynamics in resistant cancer cells and sensitize their apoptotic response. Our results point to p53 pulsing as a potentially druggable mechanism that mediates chemoresistance.

Network dynamics-based cancer panel stratification for systemic prediction of anticancer drug response.

Cancer is a complex disease involving multiple genomic alterations that disrupt the dynamic response of signaling networks. The heterogeneous nature of cancer, which results in highly variable drug response, is a major obstacle to developing effective cancer therapy. Previous studies of cancer therapeutic response mostly focus on static analysis of genome-wide alterations, thus they are unable to unravel the dynamic, network-specific origin of variation. Here we present a network dynamics-based approach to integrate cancer genomics with dynamics of biological network for drug response prediction and design of drug combination. We select the p53 network as an example and analyze its cancer-specific state transition dynamics under distinct anticancer drug treatments by attractor landscape analysis. Our results not only enable stratification of cancer into distinct drug response groups, but also reveal network-specific drug targets that maximize p53 network-mediated cell death, providing a basis to design combinatorial therapeutic strategies for distinct cancer genomic subtypes.

Natural variation in petal color in Lycoris longituba revealed by anthocyanin components.

Lycoris longituba is one of the species belonging to the Amaryllidaceae family. Despite its limited distribution, endemic to central eastern China, this species displays an exceptionally wide diversity of flower colors from purple, red, orange, to yellow, in nature. We study the natural variation of floral color in L. longituba by testing the components of water-soluble vacuolar pigments--anthocyanins--in its petals using high-performance liquid chromatography coupled with photodiode array detection and electrospray ionization mass spectrometry. Four anthocyanins were identified, cyanidin-3-sophoroside (Cy3So), cyanidin-3-xylosylglucoside (Cy3XyGlc), cyanidin-3-sambubioside (Cy3Sa), and pelargonidin-3-xylosylglucoside (Pg3XyGlc), which occur at various amounts in L. longituba petals of different colors. A multivariate analysis was used to explore the relationship between pigments and flower color. Anthocyanins have been thought to play a major role in acting as a UV screen that protects the plant's DNA from sunlight damage and attracting insects for the purpose of pollination. Thus, knowledge about the content and type of anthocyanins determining the petal coloration of Lycoris longituba will help to study the adaptive evolution of flowers and provide useful information for the ornamental breeding of this species.

Flavonoid composition and antioxidant activity of tree peony (Paeonia section moutan) yellow flowers.

Tree peony flowers are edible and traditional Chinese medicine materials. In the present study, 26 flavonoids were identified and quantified in yellow flowers of tree peony by high-performance liquid chromatography with diode array detector (HPLC-DAD) and by HPLC-electrospray ionization-mass spectrometry (HPLC-ESI-MS). Seventeen of them were first reported in flowers of tree peony, and glycosides of kaempferol, luteolin, and apigenin as well as isosalipurposide were the main flavonoids investigated. Furthermore, the petal extracts showed high antioxidant activity according to DPPH*, ABTS*(+), and OH* scavenging assays and ferric reducing antioxidant power assay. There were significant correlations between antioxidant activity and both the total polyphenol content (determined by Folin-Ciocalteu method) and the total content of quercetin, kaempferol, and luteolin glycosides. This work is valuable for elucidation of phenolic composition in tree peony flowers and for further utilization of them as functional food and medicine materials.