Arabidopsis Trithorax histone methyltransferases are redundant in regulating development and DNA methylation

Although the Trithorax histone methyltransferases ATX1–5 are known to regulate development and stress responses by catalyzing histone H3K4 methylation in Arabidopsis thaliana, it is unknown whether and how these histone methyltransferases affect DNA methylation. Here, we found that the redundant ATX1–5 proteins are not only required for plant development and viability but also for the regulation of DNA methylation. The expression and H3K4me3 levels of both RNA-directed DNA methylation (RdDM) genes (NRPE1, DCL3, IDN2, and IDP2) and active DNA demethylation genes (ROS1, DML2, and DML3) were downregulated in the atx1/2/4/5 mutant. Consistent with the facts that the active DNA demethylation pathway mediates DNA demethylationmainly at CG and CHG sites, and that the RdDM pathway mediates DNA methylation mainly at CHH sites, whole-genome DNA methylation analyses showed that hyper-CG and CHG DMRs in atx1/2/4/5 significantly overlapped with those in the DNA demethylation pathway mutant ros1 dml2 dml3 (rdd), and that hypo-CHH DMRs in atx1/2/4/5 significantly overlapped with those in the RdDM mutant nrpe1, suggesting that the ATX paralogues function redundantly to regulate DNA methylation by promoting H3K4me3 levels and expression levels of both RdDM genes and active DNA demethylation genes. Given that the ATX proteins function as catalytic subunits of COMPASS histone methyltransferase complexes, we also demonstrated that the COMPASS complex components function as a whole to regulate DNA methylation. This study reveals a previously uncharacterized mechanism underlying the regulation of DNA methylation.     

Reconstruction of tricarboxylic acid cycle in Corynebacterium glutamicum with a genome-scale metabolic network model for trans-4-hydroxyproline production

trans-4-Hydroxy- l -proline (Hyp) is an abundant component of mammalian collagen and functions as a chiral synthon for the syntheses of anti-inflammatory drugs in the pharmaceutical industry. Proline 4-hydroxylase (P4H) can catalyze the conversion of l -proline to Hyp; however, it is still challenging for the fermentative production of Hyp from glucose using P4H due to the low yield and productivity. Here, we report the metabolic engineering of Corynebacterium glutamicum for the fermentative production of Hyp by reconstructing tricarboxylic acid (TCA) cycle together with heterologously expressing the p4h gene from Dactylosporangium sp. strain RH1. In silico model-based simulation showed that α-ketoglutarate was redirected from the TCA cycle toward Hyp synthetic pathway driven by P4H when the carbon flux from succinyl-CoA to succinate descended to zero. The interruption of the TCA cycle by the deletion of sucCD-encoding the succinyl-CoA synthetase (SUCOAS) led to a 60% increase in Hyp production and had no obvious impact on the growth rate. Fine-tuning of plasmid-borne ProB* and P4H abundances led to a significant increase in the yield of Hyp on glucose. The final engineered Hyp-7 strain produced up to 21.72 g/L Hyp with a yield of 0.27 mol/mol (Hyp/glucose) and a volumetric productivity of 0.36 g·L ⁻¹·hr ⁻¹ in the shake flask fermentation. To our knowledge, this is the highest yield and productivity achieved by microbial fermentation in a glucose-minimal medium for Hyp production. This strategy provides new insights into engineering C. glutamicum by flux coupling for the fermentative production of Hyp and related products.     

Identification and functional analysis of proteins in response to light intensity,temperature and water potential in Brassica rapa hypocotyl

Hypocotyl elongation is an early event in plant growth and development and is sensitive to fluctuations in light, temperature, water potential and nutrients. Most research on hypocotyl elongation has focused on the regulatory mechanism of a single environment factor. However, information about combined effects of multi‐environment factors remains unavailable, and overlapping sites of the environmental factors signaling pathways in the regulation of hypocotyl elongation remain unclear. To identify how cross‐talks among light intensity, temperature and water potential regulate hypocotyl elongation in Brassica rapa L. ssp. chinesis, a comprehensive isobaric tag for relative and absolute quantitation‐based proteomic approach was adopted. In total, 7259 proteins were quantified, and 378 differentially expressed proteins (DEPs) were responsive to all three environmental factors. The DEPs were involved in a variety of biochemical processes, including signal transduction, cytoskeletal organization, carbohydrate metabolism, cell wall organization, protein modification and transport. The DEPs did not function in isolation, but acted in a large and complex interaction network to affect hypocotyl elongation. Among the DEPs, phyB was outstanding for its significant fold change in quantity and complex interaction networks with other proteins. In addition, changes of sensitivity to environmental factors in phyB‐9 suggested a key role in the regulation of hypocotyl elongation. Overall, the data presented in this study show a profile of proteins interaction network in response to light intensity, temperature and water potential and provides molecular basis of hypocotyl elongation in B. rapa.     

Ligularia dalaolingensis sp. nov. (Asteraceae–Senecioneae) from central China

Ligularia dalaolingensis, a new species from Hubei and Hunan, China, is described and illustrated. It belongs to L. sect. Ligularia ser. Speciosae on the basis of its palmate leaf venation, racemose synflorescence and pappus which is slightly shorter than the tube of the tubular corolla. In the series, its closest relatives are assumed to be L. fischeri and L. stenocephala. From L. fischeri, L. dalaolingensis is readily distinguished by smaller basal leaves, shorter synflorescence, narrower involucres and fewer phyllaries and florets; from L. stenocephala, L. dalaolingensis differs by smaller basal leaves, shorter synflorescence as well as broader bracts. A diagnostic key to Chinese species of L. ser. Speciosae with broadly ovate, ovate or ovate‐lanceolate bracts is provided.     

Chronic Sleep Restriction Induces Aβ Accumulation by Disrupting the Balance of Aβ Production and Clearance in Rats

Amyloid-β (Aβ) plays an important role in Alzheimer’s disease (AD) pathogenesis, and growing evidence has shown that poor sleep quality is one of the risk factors for AD, but the mechanisms of sleep deprivation leading to AD have still not been fully demonstrated. In the present study, we used wild-type (WT) rats to determine the effects of chronic sleep restriction (CSR) on Aβ accumulation. We found that CSR-21d rats had learning and memory functional decline in the Morris water maze (MWM) test. Meanwhile, Aβ₄₂ deposition in the hippocampus and the prefrontal cortex was high after a 21-day sleep restriction. Moreover, compared with the control rats, CSR rats had increased expression of β-site APP-cleaving enzyme 1 (BACE1) and sAPPβ and decreased sAPPα levels in both the hippocampus and the prefrontal cortex, and the BACE1 level was positively correlated with the Aβ₄₂ level. Additionally, in CSR-21d rats, low-density lipoprotein receptor-related protein 1 (LRP-1) levels were low, while receptor of advanced glycation end products (RAGE) levels were high in the hippocampus and the prefrontal cortex, and these transporters were significantly correlated with Aβ₄₂ levels. In addition, CSR-21d rats had decreased plasma Aβ₄₂ levels and soluble LRP1 (sLRP1) levels compared with the control rats. Altogether, this study demonstrated that 21 days of CSR could lead to brain Aβ accumulation in WT rats. The underlying mechanisms may be related to increased Aβ production via upregulation of the BACE1 pathway and disrupted Aβ clearance affecting brain and peripheral Aβ transport.

     

Effects of S-Abscisic Acid (S-ABA) on Seed Germination,Seedling Growth,and Asr1 Gene Expression Under Drought Stress in Maize

The objective of this study was to evaluate the ability of the phytohormone S-abscisic acid (S-ABA) to protect maize seedlings grown under drought stress and to measure their increased drought tolerance. The maize hybrids ‘Zhengdan 958’ (ZD958; drought tolerant) and ‘Xundan 20’ (XD20; drought sensitive) were treated with nutrient solutions of different concentrations (1, 2, 4, 8, and 10 mg/kg) of S-ABA under polyethylene glycol (PEG, 15% w/v, MW 6000) simulated drought stress. Optimal concentrations of S-ABA were designed to be sprayed onto the leaves of seedlings, and their effect on endogenous ABA, malondialdehyde (MDA), osmotic substances, antioxidant enzyme activities, and Asr1 gene expression in seedlings were studied. Results indicated that, under drought stress, S-ABA treatment significantly improved maize seed germination rate (GR), germination energy (GE), and seedling biomass (p < 0.05). After spraying 4 mg/kg S-ABA onto leaves, the endogenous hormone ABA, osmotic substances, antioxidant enzyme activities, and expressive quantity of the Asr1 gene were extended and MDA content dropped significantly (p < 0.05). Moreover, ZD 958 endogenous ABA content, osmotic substances content, antioxidant enzyme activity and Asr1 gene expressive quantity were higher than that of XD 20 (p < 0.05). In conclusion, S-ABA treatment increased the content of endogenous ABA, induced an increase in antioxidant enzyme activity and Asr1 gene expression level, reduced the oxidative damage caused by drought to maize leaves, and improved the adaptability of maize seedlings to withstand drought stress. The promoting effect of S-ABA on the drought-tolerant variety ZD 958 was more obvious (p < 0.05). These results serve as a reference for the use of S-ABA in mitigating drought stress in maize.

     

Astragaloside suppresses tumor necrosis factor receptor-associated factor 5 signaling pathway and alleviates neurodegenerative changes in retinal pigment epithelial cells induced by isoflurane

Epidemiological studies showed that isoflurane, a general anesthetic widely used in surgery including those for the children, is associated with impairment of neurodevelopment and neurodegenerative diseases, such as Alzheimer’s disease (AD) and age-related macular degeneration (AMD), which are related to the accumulation of reactive oxygen species (ROS). Astragaloside (AS) is an antioxidant derivative from a traditional Chinese herbal medicine Astragalus membraneaceus Bunge. In this study, we used retinal pigment epithelial cells, which share plenty of features with neurodegenerative diseases such as AD and AMD to investigate the effect of AS. Cell cycle re-entry and proapoptosis were seen in retinal pigment epithelium (RPE) cells treated with isoflurane, which was alleviated by pretreatment of AS. Further, tumor necrosis factor receptor-associated factor 5 (TRAF5) and downstream nuclear factor-κB (NF-κB) were investigated to elucidate the molecular mechanism underlying protective effect of AS. RPE cells exposed to isoflurane expressed higher TRAF5 and NF-κB than those pretreated with AS, suggesting a critical role of TRAF5 therein. In Morris water maze (MWM) assay, Sprague-Dawley rats pretreated with AS and then exposed to isoflurane spent less time in swimming to the platform, and their TRAF5 expression was significantly lower than those received anesthesia alone. Further studies on the consequence of forced downregulation or upregulation are warranted that may employ cutting-edge technologies such as optogenetics to overcome the difficulties in manipulating expression of TRAF5. Although the link between TRAF5 and neurodegeneration requires more in-depth investigations, our study provide a novel hint on the pathological mechanism of isoflurane and suggest a potential target for eliminating persistent side effect of anesthesia.     

Focus: The Science of Stress: PTSD Among Shidu Parents in China: The Roles of Personality Types and Social Support

Background: The psychological problems of Shidu Parents (SDP) under the China’s One-Child Policy have been documented. The purpose of this study was to investigate the relationships among personality types, social support, and post-traumatic stress disorder (PTSD) in SDP. Methods: The PTSD Checklist-Civilian Version (PCL-C), The Big Five Personality Traits (NEO), and Social Support Revalued Scale (SSRS) were administered to the sample of 149 SDP who were over 50 years old and had lost their only child more than one year ago. Results: Among SDP, mothers were more likely to develop PTSD than fathers (χ² = 11.16, p < 0.01). Parents who were extraverted had a lower risk of developing PTSD-related symptoms (χ² = 8.58, p < 0.01), and the effect of neuroticism was significant (χ² = 23.73, p < 0.01). The more social support parents utilized, the lower the incidence of PTSD (t = 4.56, p < 0.01). The result of multilevel linear regression showed that sex, neuroticism, and objective social support remained significantly different after combining all personality types and social support systems in the same model. Social support partially mediated the relationship between neuroticism and PTSD. Meanwhile, it was a complete mediator between extraversion and PTSD. Conclusions: Female sex/gender, neuroticism, and introversion were risk factors of developing PTSD, while receiving social support protected SDP from developing PTSD symptoms. Losing an only child is undoubtedly an enormous disaster for the family, which has become a huge, unavoidable social problem that must be addressed in China.