Search

In previous studies, GA20 oxidase (GA20ox) has been identified to be an important enzyme in the biosynthesis of GA, and SHOOTMERISTEMLESS (STM) can repress the expression of GA20ox. In this study, the GATA transcription factor PdeGATA3 was identified in the poplar line NL895, and its overexpression (OE) transgenic lines showed a dwarf phenotype. RNA sequencing (RNA-Seq) analysis suggested that OE PdeGATA3 could promote the expression of PdeSTM and repress the expression of PdeGA20ox. Therefore, we hypothesized that PdeGATA3 would directly promote the expression of PdeSTM and that PdeSTM would repress the expression of PdeGA20ox. Four experiments, a dual-luciferase reporter assay, GUS transient coexpression assay, yeast one-hybrid assay and electrophoretic mobility shift assay, were conducted and verified that PdeGATA3 could promote the expression of PdeSTM by binding GATA-Boxes in its promoter. OE PdeSTM in poplar resulted in a dwarf phenotype and repressed the expression of PdeGA20ox. GA measurement of the OE PdeSTM and PdeGATA3 lines showed that GA3 and GA4 contents were significantly lower than those in the wild type (WT). Accordingly, we put forward a regulation model involving plant height regulation by PdeGATA3 , PdeSTM and PdeGA20ox. [ABSTRACT FROM AUTHOR]

Magnetic particle imaging (MPI) is a radiation-free vessel- and target-imaging modality that can sensitively detect nanoparticles. A static magnetic gradient field, referred to as a selection field, is required in MPI to provide a field-free region (FFR) for spatial encoding. The image resolution of MPI is closely related to the size of the FFR, which is determined by the selection field gradient amplitude. Because of the limitations of existing gradient coil hardware, the image resolution of MPI cannot satisfy the clinical requirements of human in vivo imaging. Pulsed excitation has been confirmed to improve the image resolution of MPI by breaking down the ‘relaxation wall.’ This work proposes the use of a pulsed waveform magnetic gradient from magnetic resonance imaging to further improve the image resolution of MPI. Through alignment of the gradient direction along the field-free line (FFL), each location on the FFL is able to have a unique excitation field strength that generates a specific relaxation-induced decay signal. Through excitation of nanoparticles on the FFL with many gradient profiles, a high-resolution, one-dimensional (1D) image can be reconstructed on the FFL. For larger magnetic nanoparticles, simulation results revealed that a pulsed excitation field with a greater flat portion generates a 1D bar pattern phantom image with a higher correlation and spatial resolution. With parallel FFL and gradient coil movements, high-resolution, two-dimensional (2D) Shepp–Logan phantom and brain vessel maps were reconstructed through repetition of the spatially resolved measurement of magnetic nanoparticles on the FFL. [ABSTRACT FROM AUTHOR]

Grain weight and grain number, the two important yield traits, are mainly determined by grain size and panicle architecture in rice. Herein, we report the identification and functional analysis of OsSPL4 in panicle and grain development of rice. Using CRISPR/Cas9 system, two elite alleles of OsSPL4 were obtained, which exhibited an increasing number of grains per panicle and grain size, resulting in increase of rice yield. Cytological analysis showed that OsSPL4 could regulate spikelet development by promoting cell division. The results of RNA-seq and qRT-PCR validations also demonstrated that several MADS-box and cell-cycle genes were up-regulated in the mutation lines. Co-expression network revealed that many yield-related genes were involved in the regulation network of OsSPL4. In addition, OsSPL4 could be cleaved by the osa-miR156 in vivo, and the OsmiR156-OsSPL4 module might regulate the grain size in rice. Further analysis indicated that the large-grain allele of OsSPL4 in indica rice might introgress from aus varieties under artificial selection. Taken together, our findings suggested that OsSPL4 could be as a key regulator of grain size by acting on cell division control and provided a strategy for panicle architecture and grain size modification for yield improvement in rice. [ABSTRACT FROM AUTHOR]

Integration of transcriptomics and metabolomics data can provide detailed information for better understanding the molecular mechanisms underlying salt tolerance in rice. In the present study, we report a comprehensive analysis of the transcriptome and metabolome of rice overexpressing the OsDRAP1 gene, which encodes an ERF transcription factor and was previously identified to be conferring drought tolerance. Phenotypic analysis showed that OsDRAP1 overexpression (OE) improved salt tolerance by increasing the survival rate under salt stress. OsDRAP1 affected the physiological indices such as superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) to enhance redox homeostasis and membrane stability in response to salt stress. Higher basal expression of OsDRAP1 resulted in differential expression of genes that potentially function in intrinsic salt tolerance. A core set of genes with distinct functions in transcriptional regulation, organelle gene expression and ion transport were substantially up-regulated in the OE line in response to salt stress, implying their important role in OsDRAP1-mediated salt tolerance. Correspondingly, metabolome profiling detected a number of differentially metabolites in the OE line relative to the wild type under salt stress. These metabolites, including amino acids (proline, valine), organic acids (glyceric acid, phosphoenolpyruvic acid and ascorbic acid) and many secondary metabolites, accumulated to higher levels in the OE line, demonstrating their role in salt tolerance. Integration of transcriptome and metabolome analysis highlights the crucial role of amino acids and carbohydrate metabolism pathways in OsDRAP1-mediated salt tolerance. [ABSTRACT FROM AUTHOR]

Background: Bacterial blight, which is caused by Xanthomonas oryzae pv. oryzae (Xoo), is a devastating rice disease worldwide. Rice introgression line H471, derived from the recurrent parent Huang-Hua-Zhan (HHZ) and the donor parent PSBRC28, exhibits broad-spectrum resistance to Xoo, including to the highly virulent Xoo strain PXO99A, whereas its parents are susceptible to PXO99A. To characterize the responses to Xoo, we compared the proteome profiles of the host and pathogen in the incompatible interaction (H471 inoculated with PXO99A) and the compatible interaction (HHZ inoculated with PXO99A). Results: In this study, a total of 374 rice differentially abundant proteins (DAPs) and 117 Xoo DAPs were detected in the comparison between H471 + PXO99A and HHZ + PXO99A. Most of the Xoo DAPs related to pathogen virulence, including the outer member proteins, type III secretion system proteins, TonB-dependent receptors, and transcription activator-like effectors, were less abundant in the incompatible interaction than in the compatible interaction. The rice DAPs were mainly involved in secondary metabolic processes, including phenylalanine metabolism and the biosynthesis of flavonoids and phenylpropanoids. Additionally, some DAPs involved in the phenolic phytoalexin and salicylic acid (SA) biosynthetic pathways accumulated much more in H471 than in HHZ after the inoculation with PXO99A, suggesting that phytoalexin and SA productions were induced faster in H471 than in HHZ. Further analyses revealed that the SA content increased much more rapidly in H471 than in HHZ after the inoculation, suggesting that the SA signaling pathway was activated faster in the incompatible interaction than in the compatible interaction. Conclusions: Overall, our results indicate that during an incompatible interaction between H471 and PXO99A, rice plants prevent pathogen invasion and also initiate multi-component defense responses that inhibit disease development. [ABSTRACT FROM AUTHOR]

Antiviral therapies are integral in the fight against SARS‐CoV‐2 (i.e. severe acute respiratory syndrome coronavirus 2), the causative agent of COVID‐19. Antiviral therapeutics can be divided into categories based on how they combat the virus, including viral entry into the host cell, viral replication, protein trafficking, post‐translational processing, and immune response regulation. Drugs that target how the virus enters the cell include: Evusheld, REGEN‐COV, bamlanivimab and etesevimab, bebtelovimab, sotrovimab, Arbidol, nitazoxanide, and chloroquine. Drugs that prevent the virus from replicating include: Paxlovid, remdesivir, molnupiravir, favipiravir, ribavirin, and Kaletra. Drugs that interfere with protein trafficking and post‐translational processing include nitazoxanide and ivermectin. Lastly, drugs that target immune response regulation include interferons and the use of anti‐inflammatory drugs such as dexamethasone. Antiviral therapies offer an alternative solution for those unable or unwilling to be vaccinated and are a vital weapon in the battle against the global pandemic. Learning more about these therapies helps raise awareness in the general population about the options available to them with respect to aiding in the reduction of the severity of COVID‐19 infection. In this 'A Guide To' article, we provide an in‐depth insight into the development of antiviral therapeutics against SARS‐CoV‐2 and their ability to help fight COVID‐19. [ABSTRACT FROM AUTHOR]

Rice (Oryza sativa) is very sensitive to chilling stress at seedling and reproductive stages, whereas wild rice, O. longistaminata, tolerates non-freezing cold temperatures and has overwintering ability. Elucidating the molecular mechanisms of chilling tolerance (CT) in O. longistaminata should thus provide a basis for rice CT improvement through molecular breeding. In this study, high-throughput RNA sequencing was performed to profile global transcriptome alterations and crucial genes involved in response to long-term low temperature in O. longistaminata shoots and rhizomes subjected to 7 days of chilling stress. A total of 605 and 403 genes were respectively identified as up- and down-regulated in O. longistaminata under 7 days of chilling stress, with 354 and 371 differentially expressed genes (DEGs) found exclusively in shoots and rhizomes, respectively. GO enrichment and KEGG pathway analyses revealed that multiple transcriptional regulatory pathways were enriched in commonly induced genes in both tissues; in contrast, only the photosynthesis pathway was prevalent in genes uniquely induced in shoots, whereas several key metabolic pathways and the programmed cell death process were enriched in genes induced only in rhizomes. Further analysis of these tissue-specific DEGs showed that the CBF/DREB1 regulon and other transcription factors (TFs), including AP2/EREBPs, MYBs, and WRKYs, were synergistically involved in transcriptional regulation of chilling stress response in shoots. Different sets of TFs, such as OsERF922, OsNAC9, OsWRKY25, and WRKY74, and eight genes encoding antioxidant enzymes were exclusively activated in rhizomes under long-term low-temperature treatment. Furthermore, several cis-regulatory elements, including the ICE1-binding site, the GATA element for phytochrome regulation, and the W-box for WRKY binding, were highly abundant in both tissues, confirming the involvement of multiple regulatory genes and complex networks in the transcriptional regulation of CT in O. longistaminata. Finally, most chilling-induced genes with alternative splicing exclusive to shoots were associated with photosynthesis and regulation of gene expression, while those enriched in rhizomes were primarily related to stress signal transduction; this indicates that tissue-specific transcriptional and post-transcriptional regulation mechanisms synergistically contribute to O. longistaminata long-term CT. Our findings provide an overview of the complex regulatory networks of CT in O. longistaminata. [ABSTRACT FROM AUTHOR]

A novel modifier, 1H, 1H, 2H, 2H-Perfluorooctyltriethoxysilane (PFOES), was introduced for the covalent functionalization of graphene for the first time. TEM, XPS, FT-IR, Raman, AFM and TGA were employed to characterize the morphology and structure of the PFOES-rGO. Furthermore, PVDF/PFOES-rGO composite films with different PFOES-rGO loadings were prepared by solution mixing. The dispersion of such PFOES-rGO containing fluorine ended-groups in PVDF was effectively improved compared to graphene as SEM showed. Thus, the PFOES-rGO could nucleate the PVDF crystallization and induce the formation of nearly all β phase. The dielectric, piezoelectric and dynamic mechanical properties of the PVDF/PFOES-rGO composite films were then comprehensively studied. The dielectric (at 1 kHz) and the piezoelectric constants of the PVDF/PFOES-rGO composite film at 0.3 wt% PFOES-rGO compared with the neat PVDF was greatly improved by 370% and 80.9%, respectively. The PFOES-rGO also greatly enhanced the mechanical property of PVDF composites. It is proved the modification method for graphene used in this study is very effective. [ABSTRACT FROM AUTHOR]

We used resting-state functional magnetic resonance imaging (fMRI) to investigate changes in the thalamus functional connectivity in early and late stages of amnestic mild cognitive impairment. Data of 25 late stages of amnestic mild cognitive impairment (LMCI) patients, 30 early stages of amnestic mild cognitive impairment (EMCI) patients and 30 well-matched healthy controls (HC) were analyzed from the Alzheimer’s disease Neuroimaging Initiative (ADNI). We focused on the correlation between low frequency fMRI signal fluctuations in the thalamus and those in all other brain regions. Compared to healthy controls, we found functional connectivity between the left/right thalamus and a set of brain areas was decreased in LMCI and/or EMCI including right fusiform gyrus (FG), left and right superior temporal gyrus, left medial frontal gyrus extending into supplementary motor area, right insula, left middle temporal gyrus (MTG) extending into middle occipital gyrus (MOG). We also observed increased functional connectivity between the left/right thalamus and several regions in LMCI and/or EMCI including left FG, right MOG, left and right precuneus, right MTG and left inferior temporal gyrus. In the direct comparison between the LMCI and EMCI groups, we obtained several brain regions showed thalamus-seeded functional connectivity differences such as the precentral gyrus, hippocampus, FG and MTG. Briefly, these brain regions mentioned above were mainly located in the thalamo-related networks including thalamo-hippocampus, thalamo-temporal, thalamo-visual, and thalamo-default mode network. The decreased functional connectivity of the thalamus might suggest reduced functional integrity of thalamo-related networks and increased functional connectivity indicated that aMCI patients could use additional brain resources to compensate for the loss of cognitive function. Our study provided a new sight to understand the two important states of aMCI and revealed resting-state fMRI is an appropriate method for exploring pathophysiological changes in aMCI. [ABSTRACT FROM AUTHOR]

Peroxidase (Prx)-related genes are reported to be involved in the metabolism of hydrogen peroxide (H2O2) in plants. Here, we found that the expression of the PdePrx12 gene was upregulated in wild-type (WT) poplar line NL895 infected with the pathogens Botryosphaeria dothidea strain 3C and Alternaria alternata strain 3E. The PdePrx12 gene was cloned in the poplar line NL895 and its overexpression (OE) and reduced-expression (RE) vectors were constructed. OE and RE transgenic lines were then generated. The H2O2 content in the leaves was measured by DAB staining and spectrophotometric analysis, and the data revealed that the OE line had a reduced H2O2 content, whereas the RE line had an increased H2O2 content. These transgenic and WT plants were also inoculated with the 3C/3E pathogens. The leaf area infected by pathogen 3C/3E was determined and the OE line was found to have a larger area of infection, whereas the RE line was found to have a smaller area of infection. This result suggested PdePRX12 is involved in disease resistance in poplar. Given these results, this study demonstrated that when poplar is infected by pathogens, the expression of PdePrx12 is inhibited, leading to an increase in H2O2 content, thereby enhancing disease resistance. [ABSTRACT FROM AUTHOR]

Summary: Callus formation is important for numerous biological processes in plants. Previously, we revealed that the PdeWRKY75–PdeRBOHB module positively regulates hydrogen peroxide (H2O2) accumulation, thereby affecting callus formation in poplar.In this study, we identified and confirmed a transcription factor, PdeERF114, that interacts with PdeWRKY75 both in vitro and in vivo. Gene expression analysis identified both PdeRBOHB and PdeEXPB2 as downstream genes of PdeERF114 and PdeWRKY75. Overexpression (OE) and reduced‐expression (RE) transgenic poplar lines for these four genes were generated, and the observation of callus formation was also performed in all plant materials.We demonstrated that PdeERF114 and PdeWRKY75 formed a protein complex and that this complex could bind W‐Box motifs in the promoters of PdeRBOHB and PdeEXPB2, thereby positively regulating the expression of PdeRBOHB and PdeEXPB2. The OE/RE transgenic lines for these four genes also showed enhanced/reduced callus formation.Overall, we revealed a novel gene regulatory network for the regulation of callus formation in plants that involves four genes and regulates callus formation through two pathways: the accumulation of H2O2 in explants and the relaxation of cell walls. In the future, the four genes could be used to enhance transformation effectiveness in genetic engineering. [ABSTRACT FROM AUTHOR]

Summary: Rice grain is a poor dietary source of zinc (Zn) but the primary source of cadmium (Cd) for humans; however, the molecular mechanisms for their accumulation in rice grain remain incompletely understood.This study functionally characterized a tonoplast‐localized transporter, OsMTP1. OsMTP1 was preferentially expressed in the roots, aleurone layer, and embryo of seeds. OsMTP1 knockout decreased Zn concentration in the root cell sap, roots, aleurone layer and embryo, and subsequently increased Zn concentration in shoots and polished rice (endosperm) without yield penalty. OsMTP1 haplotype analysis revealed elite alleles associated with increased Zn level in polished rice, mostly because of the decreased OsMTP1 transcripts.OsMTP1 expression in yeast enhanced Zn tolerance but did not affect that of Cd. While OsMTP1 knockout resulted in decreased uptake, translocation and accumulation of Cd in plant and rice grain, which could be attributed to the indirect effects of altered Zn accumulation.Our results suggest that rice OsMTP1 primarily functions as a tonoplast‐localized transporter for sequestrating Zn into vacuole. OsMTP1 knockout elevated Zn concentration but prevented Cd deposition in polished rice without yield penalty. Thus, OsMTP1 is a candidate gene for enhancing Zn level and reducing Cd level in rice grains. [ABSTRACT FROM AUTHOR]

Lung adenocarcinoma (LUAD) is a deadly tumor with dynamic evolutionary process. Although much endeavors have been made in identifying the temporal patterns of cancer progression, it remains challenging to infer and interpret the molecular alterations associated with cancer development and progression. To this end, we developed a computational approach to infer the progression trajectory based on cross-sectional transcriptomic data. Analysis of the LUAD data using our approach revealed a linear trajectory with three different branches for malignant progression, and the results showed consistency in three independent cohorts. We used the progression model to elucidate the potential molecular events in LUAD progression. Further analysis showed that overexpression of BUB1B, BUB1 and BUB3 promoted tumor cell proliferation and metastases by disturbing the spindle assembly checkpoint (SAC) in the mitosis. Aberrant mitotic spindle checkpoint signaling appeared to be one of the key factors promoting LUAD progression. We found the inferred cancer trajectory allows to identify LUAD susceptibility genetic variations using genome-wide association analysis. This result shows the opportunity for combining analysis of candidate genetic factors with disease progression. Furthermore, the trajectory showed clear evident mutation accumulation and clonal expansion along with the LUAD progression. Understanding how tumors evolve and identifying mutated genes will help guide cancer management. We investigated the clonal architectures and identified distinct clones and subclones in different LUAD branches. Validation of the model in multiple independent data sets and correlation analysis with clinical results demonstrate that our method is effective and unbiased. Author summary: Lung adenocarcinoma (LUAD) is a deadly tumor that remains approximately 15% survival rate in 5 years. The diverse reasons that made cancer progression and metastasis include genetic mutation, gene expression alteration, and so on. Understanding this dynamic process and identifying pivotal molecular events driving tumor progression is essential for improving LUAD diagnosis and treatment. Studying time-series data can simulate cancer evolution and determine the temporal patterns of molecular alterations. Unfortunately, it is difficult to collect complete time-series data from individual patients due to various reasons. In this study, we developed a trajectory model based on gene expression of LUAD patients and identified distinct progression branches. Moreover, we found a key gene BUB1B that could lead to aberrant spindle assembly checkpoint (SAC) signaling, and this appeared to be one of the key factors promoting LUAD progression. The trajectory shows clear evident mutation accumulation and clonal expansion along with the LUAD progression. We also investigated the clonal architectures and identified distinct clones and subclones in different LUAD branches. This clones and subclones can be used to identify combination therapy for LUAD. Our results demonstrate the biological utility and clinical application prospects of this progression model. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is characterized by dopaminergic neurodegeneration and an abnormal accumulation of α-synuclein aggregates. A number of genetic factors have been shown to increase the risk of PD. Exploring the underlying molecular mechanisms that mediate PD's transcriptomic diversity can help us understand neurodegenerative pathogenesis. In this study, we identified 9897 A-to-I RNA editing events associated with 6286 genes across 372 PD patients. Of them, 72 RNA editing events altered miRNA binding sites and this may directly affect miRNA regulations of their host genes. However, RNA editing effects on the miRNA regulation of genes are more complex. They can (1) abolish existing miRNA binding sites, which allows miRNAs to regulate other genes; (2) create new miRNA binding sites that may sequester miRNAs from regulating other genes; or (3) occur in the miRNA seed regions and change their targets. The first two processes are also referred to as miRNA competitive binding. In our study, we found 8 RNA editing events that may alter the expression of 1146 other genes via miRNA competition. We also found one RNA editing event that modified a miRNA seed region, which was predicted to disturb the regulation of four genes. Considering the PD-related functions of the affected genes, 25 A-to-I RNA editing biomarkers for PD are proposed, including the 3 editing events in the EIF2AK2, APOL6, and miR-4477b seed regions. These biomarkers may alter the miRNA regulation of 133 PD-related genes. All these analyses reveal the potential mechanisms and regulations of RNA editing in PD pathogenesis. [ABSTRACT FROM AUTHOR]

A-to-I RNA editing diversifies human transcriptome to confer its functional effects on the downstream genes or regulations, potentially involving in neurodegenerative pathogenesis. Its variabilities are attributed to multiple regulators, including the key factor of genetic variants. To comprehensively investigate the potentials of neurodegenerative disease-susceptibility variants from the view of A-to-I RNA editing, we analyzed matched genetic and transcriptomic data of 1596 samples across nine brain tissues and whole blood from two large consortiums, Accelerating Medicines Partnership-Alzheimer's Disease and Parkinson's Progression Markers Initiative. The large-scale and genome-wide identification of 95 198 RNA editing quantitative trait loci revealed the preferred genetic effects on adjacent editing events. Furthermore, to explore the underlying mechanisms of the genetic controls of A-to-I RNA editing, several top RNA-binding proteins were pointed out, such as EIF4A3 , U2AF2 , NOP58 , FBL , NOP56 and DHX9 , since their regulations on multiple RNA-editing events were probably interfered by these genetic variants. Moreover, these variants may also contribute to the variability of other molecular phenotypes associated with RNA editing, including the functions of 3 proteins, expressions of 277 genes and splicing of 449 events. All the analyses results shown in NeuroEdQTL (https://relab.xidian.edu.cn/NeuroEdQTL/) constituted a unique resource for the understanding of neurodegenerative pathogenesis from genotypes to phenotypes related to A-to-I RNA editing. [ABSTRACT FROM AUTHOR]

SUMMARY: Phosphorus (P) is an important nutrient for plants. Here, we identify a WRKY transcription factor (TF) in poplar (Populus deltoides × Populus euramericana) (PdeWRKY65) that modulates tissue phosphate (Pi) concentrations in poplar. PdeWRKY65 overexpression (OE) transgenic lines showed reduced shoot Pi concentrations under both low and normal Pi availabilities, while PdeWRKY65 reduced expression (RE) lines showed the opposite phenotype. A gene encoding a Pi transporter (PHT), PdePHT1;9, was identified as the direct downstream target of PdeWRKY65 by RNA sequencing (RNA‐Seq). The negative regulation of PdePHT1;9 expression by PdeWRKY65 was confirmed by DNA–protein interaction assays, including yeast one‐hybrid (Y1H), electrophoretic mobility shift assay (EMSA), co‐expression of the promoters of PdePHT1;9 and PdeWRKY65 in tobacco (Nicotiana benthamiana) leaves, and chromatin immunoprecipitation–quantitative PCR. A second WRKY TF, PdeWRKY6, was subsequently identified and confirmed to positively regulate the expression of PdePHT1;9 by DNA–protein interaction assays. PdePHT1;9 and PdeWRKY6 OE and RE poplar transgenic lines were used to confirm their positive regulation of shoot Pi concentrations, under both normal and low Pi availabilities. No interaction between PdeWRKY6 and PdeWRKY65 was observed at the DNA or protein levels. Collectively, these data suggest that the low Pi‐responsive TFs PdeWRKY6 and PdeWRKY65 independently regulate the expression of PHT1;9 to modulate tissue Pi concentrations in poplar. Significance Statement: The genes PdeWRKY65 and PdeWRKY6, encoding WRKY transcription factors, and PdePHT1;9, encoding a phosphate (Pi) transporter, form a regulatory network to modulate tissue Pi concentrations in response to low Pi availability in poplar (Populus deltoides × Populus euramericana). In the regulatory network, PdeWRKY65 and PdeWRKY6 negatively and positively regulate the expression of PdePHT1;9 by binding to W‐Boxes within the PdePHT1;9 promoter, respectively. [ABSTRACT FROM AUTHOR]

The Chinese tallow tree (Triadica sebifera) can produce oil with high content of unsaturated fatty acids in seeds and shows attractive leaf color in autumn and winter. Here, the 739 Mb chromosome-scale genome sequence of the Chinese tallow tree was assembled and it reveals the Chinese tallow tree is a tetraploid. Numerous genes related to nutrition assimilation, energy utilization, biosynthesis of secondary metabolites and resistance significantly expanded or are specific to the Chinese tallow tree. These genes would enable the Chinese tallow tree to obtain high adaptability. More genes in fatty acids biosynthesis in its genome, especially for unsaturated fatty acids biosynthesis, and higher expression of these genes in seeds would be attributed to its high content of unsaturated fatty acids. Cyanidin 3-O-glucoside was identified as the major component of anthocyanin in red leaves. All structural genes in anthocyanin biosynthesis show significantly higher expression in red leaves than in green leaves. Transcription factors, seven MYB and one bHLH, were predicted to regulate these anthocyanin biosynthesis genes. Collectively, we provided insight into the polyploidization, high adaptability and biosynthesis of the high content of unsaturated fatty acids in seeds and anthocyanin in leaves for the Chinese tallow tree. A chromosome-level assembly of the economically-important Chinese tallow tree is presented alongside functional analyses into biosynthetic products in the leaves and seeds. [ABSTRACT FROM AUTHOR]

Background: Trigeminal neuralgia (TN) is a neuropathic pain that occurs in branches of the trigeminal nerve. MicroRNAs (miRNAs) have been considered key mediators of neuropathic pain. This study was aimed to elucidate the pathophysiological function and mechanisms of miR‐223‐3p in mouse models of TN. Methods: Infraorbital nerve chronic constriction injury (CCI‐ION) was applied in male C57BL/6J mice to establish mouse models of TN. Pain responses were assessed utilizing Von Frey method. The expression of miR‐223‐3p, MKNK2, and MAPK/ERK pathway protein in trigeminal ganglions (TGs) of CCI‐ION mice was measured using RT‐qPCR and Western blotting. The concentrations of inflammatory cytokines were evaluated using Western blotting. The relationship between miR‐223‐3p and MKNK2 was tested by a luciferase reporter assay. Results: We found that miR‐223‐3p was downregulated, while MKNK2 was upregulated in TGs of CCI‐ION mice. MiR‐223‐3p overexpression by an intracerebroventricular injection of Lv‐miR‐223‐3p attenuated trigeminal neuropathic pain in CCI‐ION mice, as well as reduced the protein levels of pro‐inflammatory cytokines in TGs of CCI‐ION mice. MKNK2 was verified to be targeted by miR‐223‐3p. Additionally, miR‐223‐3p overexpression decreased the phosphorylation levels of ERK1/2, JNK, and p38 protein in TGs of CCI‐ION mice to inhibit MAPK/ERK signaling. Conclusions: Overall, miR‐223‐3p attenuates the development of TN by targeting MKNK2 to suppress MAPK/ERK signaling. [ABSTRACT FROM AUTHOR]

Hydrogen peroxide (H2O2) plays important roles in plant development. Adventitious roots (AR), lateral buds (LB) and callus formation are important traits for plants. Here, a gene encoding RESPIRATORY BURST OXIDASE HOMOLOG B (PdeRBOHB) from poplar line 'NL895' (Populus. deltoides × P. euramericana) was predicted to be involved in H2O2 accumulation, and lines with reduced expression were generated. H2O2 content was decreased, and the development of adventitious roots, lateral buds, and callus was inhibited in reduced expression PdeRBOHB lines. A gene encoding PdeWRKY75 was identified as the upstream transcription factor positively regulating PdeRBOHB. This regulation was confirmed by dual luciferase reporter assay, GUS transient expression analysis and electrophoretic mobility shift assay. In the reduced expression PdeWRKY75 lines, H2O2 content was decreased and the development of adventitious roots, lateral buds, and callus development was inhibited, while in the overexpression lines, H2O2 content was increased and the development of adventitious roots and lateral buds was inhibited, but callus formation was enhanced. Additionally, reduced expression PdeRBOHB lines showed lowered expression of PdeWRKY75 , while exogenous application of H2O2 showed the opposite effect. Together, these results suggest that PdeWRKY75 and PdeRBOHB are part of a regulatory module in H2O2 accumulation, which is involved in the regulation of multiple biological processes. [ABSTRACT FROM AUTHOR]

Ovarian tumor (OTU) subfamily deubiquitinases are involved in various cellular processes, such as inflammation, ferroptosis and tumorigenesis; however, their pathological roles in prostate cancer (PCa) remain largely unexplored. In this study, we observed that several OTU members displayed genomic amplification in PCa, among which ovarian tumor deubiquitinase 6A (OTUD6A) amplified in the top around 15–20%. Further clinical investigation showed that the OTUD6A protein was highly expressed in prostate tumors, and increased OTUD6A expression correlated with a higher biochemical recurrence risk after prostatectomy. Biologically, wild-type but not a catalytically inactive mutant form of OTUD6A was required for PCa cell progression. In vivo experiments demonstrated that OTUD6A oligonucleotides markedly suppressed prostate tumorigenesis in PtenPC−/− mice and patient-derived xenograft (PDX) models. Mechanistically, the SWI/SNF ATPase subunit Brg1 and the nuclear receptor AR (androgen receptor) were identified as essential substrates for OTUD6A in PCa cells by a mass spectrometry (MS) screening approach. Furthermore, OTUD6A stabilized these two proteins by erasing the K27-linked polyubiquitination of Brg1 and K11-linked polyubiquitination of AR. OTUD6A amplification exhibited strong mutual exclusivity with mutations in the tumor suppressors FBXW7 and SPOP. Collectively, our results indicate the therapeutic potential of targeting OTUD6A as a deubiquitinase of Brg1 and AR for PCa treatment. OTUD6A, a deubiquitinase, is amplified in prostate cancer and correlates with poor survivability, increasing the growth of prostate cancer cell lines and PDX models. OTUD6A stabilizes the expression of Brg1 and AR through the removal of K27- and K11-linked polyubiquination. [ABSTRACT FROM AUTHOR]

Xanthomonas oryzae pv. oryzae (Xoo) is the causal agent of rice bacterial blight, which is a major rice disease in tropical Asian countries. An attempt has been made to investigate gene expression patterns of three Xoo strains on the minimal medium XOM2, PXO99 (P6) and PXO86 (P2) from the Philippines, and GD1358 (C5) from China, which exhibited different virulence in 30 rice varieties, with putative virulence factors using deep sequencing. In total, 4,781 transcripts were identified in this study, and 1,151 and 3,076 genes were differentially expressed when P6 was compared with P2 and with C5, respectively. Our results indicated that Xoo strains from different regions exhibited distinctly different expression patterns of putative virulence-relevant genes. Interestingly, 40 and 44 genes involved in chemotaxis and motility exhibited higher transcript alterations in C5 compared with P6 and P2, respectively. Most other genes associated with virulence, including exopolysaccharide (EPS) synthesis, Hrp genes and type III effectors, including Xanthomonas outer protein (Xop) effectors and transcription activator-like (TAL) effectors, were down-regulated in C5 compared with P6 and P2. The data were confirmed by real-time quantitative RT-PCR, tests of bacterial motility, and enzyme activity analysis of EPS and xylanase. These results highlight the complexity of Xoo and offer new avenues for improving our understanding of Xoo-rice interactions and the evolution of Xoo virulence. [ABSTRACT FROM AUTHOR]

Sorghum (Sorghum bicolor) is one of the world's most important cereal crops. S. propinquum is a perennial wild relative of S. bicolor with well-developed rhizomes. Functional genomics analysis of S. propinquum, especially with respect to molecular mechanisms related to rhizome growth and development, can contribute to the development of more sustainable grain, forage, and bioenergy cropping systems. In this study, we used a whole rice genome oligonucleotide microarray to obtain tissue-specific gene expression profiles of S. propinquum with special emphasis on rhizome development. A total of 548 tissue-enriched genes were detected, including 31 and 114 unique genes that were expressed predominantly in the rhizome tips (RT) and internodes (RI), respectively. Further GO analysis indicated that the functions of these tissue-enriched genes corresponded to their characteristic biological processes. A few distinct cis-elements, including ABA-responsive RY repeat CATGCA, sugar-repressive TTATCC, and GA-responsive TAACAA, were found to be prevalent in RT-enriched genes, implying an important role in rhizome growth and development. Comprehensive comparative analysis of these rhizome-enriched genes and rhizome-specific genes previously identified in Oryza longistaminata and S. propinquum indicated that phytohormones, including ABA, GA, and SA, are key regulators of gene expression during rhizome development. Co-localization of rhizome-enriched genes with rhizome-related QTLs in rice and sorghum generated functional candidates for future cloning of genes associated with rhizome growth and development. [ABSTRACT FROM AUTHOR]

Connected consciousness refers to the state when external stimuli can enter into the stream of our consciousness experience. Emerging evidence suggests that although patients may not respond behaviorally to external stimuli during anesthesia, they may be aware of their surroundings. In this work, we investigated whether EEG based brain decoding could be used for detecting connected consciousness in the absence of behavioral responses during propofol infusion. A total of 14 subjects participated in our experiment. Subjects were asked to discriminate two types of auditory stimuli with a finger press during an ultraslow propofol infusion. We trained an EEG based brain decoding model using data collected in the awakened state using the same auditory stimuli and tested the model on data collected during the propofol infusion. The model provided a correct classification rate (CCR) of 7 8. 7 4 ± 1 1. 1 5 % when subjects were able to respond to the stimuli during the propofol infusion. The CCR dropped to 6 7. 2 9 ± 8. 2 1 % when subjects ceased responding and further decreased to 5 8. 1 1 ± 8. 1 5 % when we increased the propofol concentration by another 0.2 μ g/ml. After terminating the propofol infusion, we observed that the CCR rebounded to 6 5. 3 1 ± 7. 1 1 % before the subjects regained consciousness. With the classification results, we provided evidence that loss of consciousness is a gradual process and may progress from full consciousness to connected consciousness and then to disconnected consciousness. [ABSTRACT FROM AUTHOR]

• Response time evaluates responsiveness levels continuously during slow propofol induction. • Time-resolved spectral slope correlates better with RT at the beta-gamma band. • Frontal spectral slopes perform best for predicting response time. • Spectral slope decreases during anesthesia induction and increases during recovery. The level of consciousness undergoes continuous alterations during anesthesia. Prior to the onset of propofol-induced complete unconsciousness, degraded levels of behavioral responsiveness can be observed. However, a reliable index to monitor altered consciousness levels during anesthesia has not been sufficiently investigated. In this study, we obtained 60-channel EEG data from 24 healthy participants during an ultra-slow propofol infusion protocol starting with an initial concentration of 1 μg/ml and a stepwise increase of 0.2 μg/ml in concentration. Consecutive auditory stimuli were delivered every 5 to 6 s, and the response time to the stimuli was used to assess the responsiveness levels. We calculated the spectral slope in a time-resolved manner by extracting 5-second EEG segments at each auditory stimulus and estimated their correlation with the corresponding response time. Our results demonstrated that during slow propofol infusion, the response time to external stimuli increased, while the EEG spectral slope, fitted at 15–45 Hz, became steeper, and a significant negative correlation was observed between them. Moreover, the spectral slope further steepened at deeper anesthetic levels and became flatter during anesthesia recovery. We verified these findings using an external dataset. Additionally, we found that the spectral slope of frontal electrodes over the prefrontal lobe had the best performance in predicting the response time. Overall, this study used a time-resolved analysis to suggest that the EEG spectral slope could reliably track continuously altered consciousness levels during propofol anesthesia. Furthermore, the frontal spectral slope may be a promising index for clinical monitoring of anesthesia depth. [ABSTRACT FROM AUTHOR]

BACKGROUND: A large proportion of gastric cancer patients are susceptible to chemoresistance, while the underlying mechanism remains obscure. Stress granules (SGs) play a self-defence role for tumour cells in inhibiting chemotherapy-induced apoptosis. As an SG assembly effector, G3BP1 (Ras-GTPase-activating protein SH3 domain-binding protein) has been reported to be overexpressed in gastric cancer; thus, here we aim to explore its potent roles in gastric cancer chemoresistance. METHODS: Kaplan–Meier analysis was used to compare survival rates in gastric cancer patients with different G3BP1 expression. The influence of G3BP1 on gastric cancer cell chemoresistance and apoptosis were evaluated by in vitro and in vivo approaches. The interaction between G3BP1 and YWHAZ was assessed by immunohistochemistry, immunoprecipitation and immunofluorescence. RESULTS: G3BP1 was associated with the poor outcome of gastric cancer patients who received adjuvant chemotherapy. G3BP1 knockdown significantly increased the sensitivity of gastric cancer cells to chemotherapy drugs. Mechanically, cell apoptosis and pro-apoptotic-associated molecules were significantly elevated upon G3BP1 depletion. Gene co-expression network analyses identified YWHAZ as the critical interlayer of G3BP1; as a result, G3BP1 interacted with YWHAZ to sequester Bax into the cytoplasm. Clinically, G3BP1highYWHAZhigh gastric cancer patients displayed the worst outcome compared with other patients after chemotherapy. CONCLUSIONS: The expression of G3BP1 and YWHAZ could predict the adjuvant chemotherapy benefit in gastric cancer patients. [ABSTRACT FROM AUTHOR]

Background: A large proportion of gastric cancer patients are susceptible to chemoresistance, while the underlying mechanism remains obscure. Stress granules (SGs) play a self-defence role for tumour cells in inhibiting chemotherapy-induced apoptosis. As an SG assembly effector, G3BP1 (Ras-GTPase-activating protein SH3 domain-binding protein) has been reported to be overexpressed in gastric cancer; thus, here we aim to explore its potent roles in gastric cancer chemoresistance.Methods: Kaplan-Meier analysis was used to compare survival rates in gastric cancer patients with different G3BP1 expression. The influence of G3BP1 on gastric cancer cell chemoresistance and apoptosis were evaluated by in vitro and in vivo approaches. The interaction between G3BP1 and YWHAZ was assessed by immunohistochemistry, immunoprecipitation and immunofluorescence.Results: G3BP1 was associated with the poor outcome of gastric cancer patients who received adjuvant chemotherapy. G3BP1 knockdown significantly increased the sensitivity of gastric cancer cells to chemotherapy drugs. Mechanically, cell apoptosis and pro-apoptotic-associated molecules were significantly elevated upon G3BP1 depletion. Gene co-expression network analyses identified YWHAZ as the critical interlayer of G3BP1; as a result, G3BP1 interacted with YWHAZ to sequester Bax into the cytoplasm. Clinically, G3BP1highYWHAZhigh gastric cancer patients displayed the worst outcome compared with other patients after chemotherapy.Conclusions: The expression of G3BP1 and YWHAZ could predict the adjuvant chemotherapy benefit in gastric cancer patients. [ABSTRACT FROM AUTHOR]

Background: Salt stress and bacterial blight caused by Xanthomonas oryzae pv. oryzae (Xoo) are key limiting factors of rice (Oryza sativa L.) yields. Members of sucrose non-fermenting 1 (SNF1)-related protein kinase 2 (SnRK2), which is a family of plant-specific Ser/Thr kinases, are important components of signaling pathways involved in plant developmental processes and responses to stresses. There are 10 members of the SnRK2 family in rice; however, their functions are poorly understood, as are the underlying molecular mechanisms. Results: In this study, we found that OsSAPK9, which belongs to the SnRK2 family, positively regulated salt-stress tolerance and strain-specific resistance to bacterial blight in rice. RNA sequencing revealed that there were 404 and 1324 genes differentially expressed in OsSAPK9-RNAi in comparison with wild-type plants under salt-stress conditions and after Xoo inoculation, respectively, which participate in basic metabolic processes. In total, 65 common differentially expressed genes involved mainly in defense responses were detected both under salt-stress conditions and after Xoo inoculation. Moreover, in vivo and in vitro experiments demonstrated that OsSAPK9 forms a protein complex with the molecular chaperones OsSGT1 and OsHsp90, and transgenic plants overexpressing OsSGT1 exhibited decreased tolerances to salt stress and significantly increased resistance levels to bacterial blight. Thus, OsSAPK9 may function as a center node regulator of salt-stress responses and disease-resistance pathways through its interaction with OsSGT1 in rice. Conclusion: This study confirms that OsSAPK9 functions as a positive regulator of salt-stress responses and disease resistance through its interaction with OsSGT1 in rice. [ABSTRACT FROM AUTHOR]

Background: High soil salinity can cause significant losses in rice productivity worldwide, mainly because salt inhibits plant growth and reduces grain yield. To cope with environmental changes, plants have evolved several adaptive mechanisms that involve the regulation of many stress-responsive genes. Results: In this study, we identified OsSTAP1, which encodes an AP2/ERF-type transcription factor, was rapidly induced by ABA, ACC, salt, cold, and PEG treatments. OsSTAP1 is localized to the nucleus and acts as a transcriptional activator in plant cells. Compared with wild type, transgenic lines overexpressing OsSTAP1 exhibited increased tolerance to salt stress with higher SOD, POD, and CAT activities, and lower Na+/K+ ratios in the shoots. In addition, many other stress-responsive genes, including other ERF- and peroxidase-encoding genes, were upregulated in the OsSTAP1-overexpression lines. Conclusion: This study suggests that OsSTAP1 functions as an AP2/ERF transcriptional activator, and plays a positive role in salt tolerance by decreasing the Na+/K+ ratio and maintaining cellular redox homeostasis. [ABSTRACT FROM AUTHOR]

Insulin signaling is mediated by a highly integrated network that controls glucose metabolism, protein synthesis, cell growth, and differentiation. Our previous work indicates that the insulin receptor tyrosine kinase substrate (IRTKS), also known as BAI1-associated protein 2-like 1 (BAIAP2L1), is a novel regulator of insulin network, but the mechanism has not been fully studied. In this work we reveal that IRTKS co-localizes with Src homology (SH2) containing inositol polyphosphate 5-phosphatase-2 (SHIP2), and the SH3 domain of IRTKS directly binds to SHIP2's catalytic domain INPP5c. IRTKS suppresses SHIP2 phosphatase to convert phosphatidylinositol 3,4,5-triphosphate (PI(3,4,5)P3, PIP3) to phosphatidylinositol (3,4) bisphosphate (PI(3,4)P2). IRTKS-knockout significantly increases PI(3,4)P2 level and decreases cellular PI(3,4,5)P3 content. Interestingly, the interaction between IRTKS and SHIP2 is dynamically regulated by insulin, which feeds back and affects the tyrosine phosphorylation of IRTKS. Furthermore, IRTKS overexpression elevates PIP3, activates the AKT–mTOR signaling pathway, and increases cell proliferation. Thereby, IRTKS not only associates with insulin receptors to activate PI3K but also interacts with SHIP2 to suppress its activity, leading to PIP3 accumulation and the activation of the AKT–mTOR signaling pathway to modulate cell proliferation. [ABSTRACT FROM AUTHOR]

The surgical treatment of congenital heart disease requires navigational assistance with transesophageal echocardiography (TEE); however, TEE images are often difficult to interpret and provide very limited anatomical information. Registering preoperative CT images to intraoperative TEE images provides surgeons with richer and more useful anatomical information. Yet, CT and TEE images differ substantially in terms of scale and geometry. In the present research, we propose a novel method for the registration of CT and TEE images for navigation during surgical repair of large defects in patients with congenital heart disease. Valve data was used for the coarse registration to determine the basic location. This was followed by the use of an enhanced probability model map to overcome gray-level differences between the two imaging modalities. Finally, the rapid optimization of mutual information was achieved by migrating parameters. This method was tested on a dataset of 240 images from 12 infant, children (≤ 3 years old), and adult patients with congenital heart disease. Compared to the “bronze standard” registration, the proposed method was more accurate with an average Dice coefficient of 0.91 and an average root mean square of target registration error of 1.2655 mm. [ABSTRACT FROM AUTHOR]

The article focuses on the African wild rice oryza, with topics including plants gene expression, rice diseases, and the rice varieties.

Physiological and emotional stressors are associated with or provoke each migraine attack and cause structural and functional changes in the central nervous system. The hippocampus, a limbic structure important in anxiety-related behavior, is vulnerable to long-term stress. Given that catechol- O-methyltransferase (COMT) is widely distributed in the hippocampus and its genetic variation is thought to contribute to the interindividual variability in pain perception and anxiety regulation, whether or not migraine and COMT val158met genotype have an interactive effect in the key brain area related to maladaptive stress, the hippocampus, is still poorly understood. Using T1-weighted and resting functional MRI, we evaluated the effect of COMT genetic variations on migraine and possible interactions between COMT and the disease in brain structure and function in 135 females with migraine without aura (MWoA) and 111 matched health controls (HC). Optimized voxel-based morphometry (VBM) and functional connectivity (FC) analyses were applied. From the whole brain VBM analysis, we found a significant disease × genotype interaction in the hippocampus, which overlapped with disease-related increase of gray matter (GM) in val homozygote migraineurs. In our results, increased GM in the hippocampus was only found in val homozygote MWoA compared to val homozygote HC. Moreover, FC between the hippocampus and the medial prefrontal cortex was significantly decreased in val homozygotes, and it was negatively correlated with self-rating anxiety scale values.Our results indicated that brain structure and function of the hippocampus are differentially affected by migraine in val homozygotes compared with met carriers. Hum Brain Mapp 36:1782-1795, 2015. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background: This study aimed to confirm that blocking RasGRP4 can effectively slow down the growth of DLBCL both in vitro and in vivo and ascertain the role of RasGRP4 in the prognosis of DLBCL clinically. Methods: RasGRP4 expression levels were examined in benign tissues and lymphomas. In order to verify somatic mutation in RasGRP4 gene, cDNA sequencing was performed in DLBCL patients. RasGRP4-dependent cell proliferation, mitochondrial membrane potential, oxidative stress levels and signaling pathway changes were measured by knockdown of RasGRP4. Tumor growth was monitored in xenografted lymphoma model. Clinical data were collected to confirm the role of RasGRP4 in DLBCL. Results: RasGRP4 expression was significantly elevated in DLBCL while no somatic mutations were detected of this gene in DLBCL patients. Decreased RasGRP4 significantly inhibited cell proliferation by simultaneously reducing mitosis and promoting apoptosis and increased the oxidative stress levels. Mechanistically, reduced expression of RasGRP4 decreased ERK while increased JNK expression in SUDHL-4 cells. Knockdown of RasGRP4 also significantly inhibited tumor formation in vivo. Furthermore, RasGRP4 expression levels were significantly higher in patients with larger DLBCL lesions (P = 0.0004), high-risk international prognostic index score groups (P = 0.0042), and its expression was positively correlated with maximum standardized uptake value in DLBCL (P = 0.0004). Conclusions: These findings indicate the oncogenic role of RasGRP4 in DLBCL, suggesting it as a prognostic biomarker and potential therapeutic target in DLBCL. [ABSTRACT FROM AUTHOR]

It is difficult to accurately assess axillary lymph nodes metastasis and the diagnosis of axillary lymph nodes in patients with breast cancer is invasive and has low-sensitivity preoperatively. This study aims to develop a mammography-based radiomics nomogram for the preoperative prediction of ALN metastasis in patients with breast cancer. This study enrolled 147 patients with clinicopathologically confirmed breast cancer and preoperative mammography. Features were extracted from each patient's mammography images. The least absolute shrinkage and selection operator regression method was used to select features and build a signature in the primary cohort. The performance of the signature was assessed using support vector machines. We developed a nomogram by incorporating the signature with the clinicopathologic risk factors. The nomogram performance was estimated by its calibration ability in the primary and validation cohorts. The signature was consisted of 10 selected ALN-status-related features. The AUC of the signature from the primary cohort was 0.895 (95% CI, 0.887-0.909) and 0.875 (95% CI, 0.698-0.891) for the validation cohort. The C-Index of the nomogram from the primary cohort was 0.779 (95% CI, 0.752-0.793) and 0.809 (95% CI, 0.794-0.833) for the validation cohort. Our nomogram is a reliable and non-invasive tool for preoperative prediction of ALN status and can be used to optimize current treatment strategy for breast cancer patients. [ABSTRACT FROM AUTHOR]