Programming of Plant Leaf Senescence with Temporal and Inter-Organellar Coordination of Transcriptome in Arabidopsis.

Plant leaves, harvesting light energy and fixing CO2, are a major source of foods on the earth. Leaves undergo developmental and physiological shifts during their lifespan, ending with senescence and death. We characterized the key regulatory features of the leaf transcriptome during aging by analyzing total- and small-RNA transcriptomes throughout the lifespan of Arabidopsis (Arabidopsis thaliana) leaves at multidimensions, including age, RNA-type, and organelle. Intriguingly, senescing leaves showed more coordinated temporal changes in transcriptomes than growing leaves, with sophisticated regulatory networks comprising transcription factors and diverse small regulatory RNAs. The chloroplast transcriptome, but not the mitochondrial transcriptome, showed major changes during leaf aging, with a strongly shared expression pattern of nuclear transcripts encoding chloroplast-targeted proteins. Thus, unlike animal aging, leaf senescence proceeds with tight temporal and distinct interorganellar coordination of various transcriptomes that would be critical for the highly regulated degeneration and nutrient recycling contributing to plant fitness and productivity.

Study on the Sodium-Doped Titania Interface-Type Memristor.

Memristors integrated into a crossbar-array architecture (CAA) are promising candidates for analog in-memory computing accelerators. However, the relatively low reliability of the memristor device and sneak current issues in CAA remain the main obstacles. Alkali ion-based interface-type memristors are promising solutions for implementing highly reliable memristor devices and neuromorphic hardware. This interface-type device benefits from self-rectifying and forming-free resistive switching (RS), and exhibits relatively low variation from device to device and cycle to cycle. In a previous report, we introduced an in situ grown Na/TiO2 memristor using atomic layer deposition (ALD) and proposed a RS mechanism from experimentally measured Schottky barrier modulation. Self-rectifying RS characteristics were observed by the asymmetric distribution of Na dopants and oxygen vacancies as the Ti metal used as the adhesion layer for the bottom electrode diffuses over the Pt electrode at 250 °C during the ALD process and is doped into the TiO2 layer. Here, we theoretically verify the modulation of the Schottky barrier at the TiO2/Pt electrode interface by Na ions. This study fabricated a Pt/Na/TiO2/Pt memristor device and confirmed its self-rectifying RS characteristics and stable retention characteristics for 24 h at 85 °C. Additionally, this device exhibited relative standard deviations of 27 and 7% in the high and low resistance states, respectively, in terms of cycle-to-cycle variation. To verify the RS mechanism, we conducted density functional theory simulations to analyze the impact of Na cations at interstitial sites on the Schottky barrier. Our findings can contribute to both fundamental understanding and the design of high-performance memristor devices for neuromorphic computing.

TOFSIMS-P: a web-based platform for analysis of large-scale TOF-SIMS data.

Time-of-flight secondary ion mass spectrometry (TOF-SIMS) has been a useful tool to profile secondary ions from the near surface region of specimens with its high molecular specificity and submicrometer spatial resolution. However, the TOF-SIMS analysis of even a moderately large size of samples has been hampered due to the lack of tools for automatically analyzing the huge amount of TOF-SIMS data. Here, we present a computational platform to automatically identify and align peaks, find discriminatory ions, build a classifier, and construct networks describing differential metabolic pathways. To demonstrate the utility of the platform, we analyzed 43 data sets generated from seven gastric cancer and eight normal tissues using TOF-SIMS. A total of 87 138 ions were detected from the 43 data sets by TOF-SIMS. We selected and then aligned 1286 ions. Among them, we found the 66 ions discriminating gastric cancer tissues from normal ones. Using these 66 ions, we then built a partial least square-discriminant analysis (PLS-DA) model resulting in a misclassification error rate of 0.024. Finally, network analysis of the 66 ions showed disregulation of amino acid metabolism in the gastric cancer tissues. The results show that the proposed framework was effective in analyzing TOF-SIMS data from a moderately large size of samples, resulting in discrimination of gastric cancer tissues from normal tissues and identification of biomarker candidates associated with the amino acid metabolism.

Wnt3a disrupts GR-TEAD4-PPARγ2 positive circuits and cytoskeletal rearrangement in a ß-catenin-dependent manner during early adipogenesis.

Adipogenesis is a process which induces or represses many genes in a way to drive irreversible changes of cell phenotypes; lipid accumulation, round cell-shape, secreting many adipokines. As a master transcription factor (TF), PPARγ2 induces several target genes to orchestrate these adipogenic changes. Thus induction of Pparg2 gene is tightly regulated by many adipogenic and also anti-adipogenic factors. Four hours after the treatment of adipogenic hormones, more than fifteen TFs including glucocorticoid receptor (GR), C/EBPß and AP-1 cooperatively bind the promoter of Pparg2 gene covering 400 bps, termed "hotspot". In this study, we show that TEA domain family transcription factor (TEAD)4 reinforces occupancy of both GR and C/EBPß on the hotspot of Pparg2 during early adipogenesis. Our findings that TEAD4 requires GR for its expression and for the ability to bind its own promoter and the hotspot region of Pparg2 gene indicate that GR is a common component of two positive circuits, which regulates the expression of both Tead4 and Pparg2. Wnt3a disrupts these mutually related positive circuits by limiting the nuclear location of GR in a ß-catenin dependent manner. The antagonistic effects of ß-catenin extend to cytoskeletal remodeling during the early phase of adipogenesis. GR is necessary for the rearrangements of both cytoskeleton and chromatin of Pparg2, whereas Wnt3a inhibits both processes in a ß-catenin-dependent manner. Our results suggest that hotspot formation during early adipogenesis is related to cytoskeletal remodeling, which is regulated by the antagonistic action of GR and ß-catenin, and that Wnt3a reinforces ß-catenin function.

Systematic analysis of expression signatures of neuronal subpopulations in the VTA.

Gene expression profiling across various brain areas at the single-cell resolution enables the identification of molecular markers of neuronal subpopulations and comprehensive characterization of their functional roles. Despite the scientific importance and experimental versatility, systematic methods to analyze such data have not been established yet. To this end, we developed a statistical approach based on in situ hybridization data in the Allen Brain Atlas and thereby identified specific genes for each type of neuron in the ventral tegmental area (VTA). This approach also allowed us to demarcate subregions within the VTA comprising specific neuronal subpopulations. We further identified WW domain-containing oxidoreductase as a molecular marker of a population of VTA neurons that co-express tyrosine hydroxylase and vesicular glutamate transporter 2, and confirmed their region-specific distribution by immunohistochemistry. The results demonstrate the utility of our analytical approach for uncovering expression signatures representing specific cell types and neuronal subpopulations enriched in a given brain area.

DBPs removal in GAC filter-adsorber.

A rapid sand filter and granular activated carbon filter-adsorber (GAC FA) were compared in terms of dissolved organic carbon (DOC) and disinfection by-products (DBPs) removal. A water treatment plant (WTP) that had a high ammonia concentration and DOC in raw water, which, in turn, led to a high concentration of DBPs because of a high dose of pre-chlorination, was investigated. To remove DBPs and DOC simultaneously, a conventional rapid sand filter had been retrofitted to a GAC FA at the Buyeo WTP in Korea. The overall removal efficiency of DBPs and DOC was higher in the GAC FA than in the sand filter, as expected. Breakthrough of trihalomethanes (THMs) was noticed after 3 months of GAC FA operation, and then removal of THMs was minimal (<10%). On the other hand, the removal efficiency of five haloacetic acids (HAA(5)) in the GAC FA was better than that of THMs, though adsorption of HAA(5) decreased rapidly after 3.5 months of GAC FA operation. And then, gradual improvement (>90%) in HAA(5) removal efficiency was again observed, which could be attributed to biodegradation. At the early stage of GAC FA operation, HAA(5) removal was largely due to physical adsorption, but later on biodegradation appeared to prevail. Biodegradation of HAA(5) was significantly influenced by water temperature. Similar turbidity removal was noticed in both filters, while better manganese removal was confirmed in the sand filter rather than in the GAC FA.

Multi-dimensional TOF-SIMS analysis for effective profiling of disease-related ions from the tissue surface.

Time-of-flight secondary ion mass spectrometry (TOF-SIMS) emerges as a promising tool to identify the ions (small molecules) indicative of disease states from the surface of patient tissues. In TOF-SIMS analysis, an enhanced ionization of surface molecules is critical to increase the number of detected ions. Several methods have been developed to enhance ionization capability. However, how these methods improve identification of disease-related ions has not been systematically explored. Here, we present a multi-dimensional SIMS (MD-SIMS) that combines conventional TOF-SIMS and metal-assisted SIMS (MetA-SIMS). Using this approach, we analyzed cancer and adjacent normal tissues first by TOF-SIMS and subsequently by MetA-SIMS. In total, TOF- and MetA-SIMS detected 632 and 959 ions, respectively. Among them, 426 were commonly detected by both methods, while 206 and 533 were detected uniquely by TOF- and MetA-SIMS, respectively. Of the 426 commonly detected ions, 250 increased in their intensities by MetA-SIMS, whereas 176 decreased. The integrated analysis of the ions detected by the two methods resulted in an increased number of discriminatory ions leading to an enhanced separation between cancer and normal tissues. Therefore, the results show that MD-SIMS can be a useful approach to provide a comprehensive list of discriminatory ions indicative of disease states.

Comprehensive data resources and analytical tools for pathological association of aminoacyl tRNA synthetases with cancer.

Mammalian cells have cytoplasmic and mitochondrial aminoacyl-tRNA synthetases (ARSs) that catalyze aminoacylation of tRNAs during protein synthesis. Despite their housekeeping functions in protein synthesis, recently, ARSs and ARS-interacting multifunctional proteins (AIMPs) have been shown to play important roles in disease pathogenesis through their interactions with disease-related molecules. However, there are lacks of data resources and analytical tools that can be used to examine disease associations of ARS/AIMPs. Here, we developed an Integrated Database for ARSs (IDA), a resource database including cancer genomic/proteomic and interaction data of ARS/AIMPs. IDA includes mRNA expression, somatic mutation, copy number variation and phosphorylation data of ARS/AIMPs and their interacting proteins in various cancers. IDA further includes an array of analytical tools for exploration of disease association of ARS/AIMPs, identification of disease-associated ARS/AIMP interactors and reconstruction of ARS-dependent disease-perturbed network models. Therefore, IDA provides both comprehensive data resources and analytical tools for understanding potential roles of ARS/AIMPs in cancers.

iNID: an analytical framework for identifying network models for interplays among developmental signaling in Arabidopsis.

Integration of internal and external cues into developmental programs is indispensable for growth and development of plants, which involve complex interplays among signaling pathways activated by the internal and external factors (IEFs). However, decoding these complex interplays is still challenging. Here, we present a web-based platform that identifies key regulators and Network models delineating Interplays among Developmental signaling (iNID) in Arabidopsis. iNID provides a comprehensive resource of (1) transcriptomes previously collected under the conditions treated with a broad spectrum of IEFs and (2) protein and genetic interactome data in Arabidopsis. In addition, iNID provides an array of tools for identifying key regulators and network models related to interplays among IEFs using transcriptome and interactome data. To demonstrate the utility of iNID, we investigated the interplays of (1) phytohormones and light and (2) phytohormones and biotic stresses. The results revealed 34 potential regulators of the interplays, some of which have not been reported in association with the interplays, and also network models that delineate the involvement of the 34 regulators in the interplays, providing novel insights into the interplays collectively defined by phytohormones, light, and biotic stresses. We then experimentally verified that BME3 and TEM1, among the selected regulators, are involved in the auxin-brassinosteroid (BR)-blue light interplay. Therefore, iNID serves as a useful tool to provide a basis for understanding interplays among IEFs.

EVpedia: an integrated database of high-throughput data for systemic analyses of extracellular vesicles.

Secretion of extracellular vesicles is a general cellular activity that spans the range from simple unicellular organisms (e.g. archaea; Gram-positive and Gram-negative bacteria) to complex multicellular ones, suggesting that this extracellular vesicle-mediated communication is evolutionarily conserved. Extracellular vesicles are spherical bilayered proteolipids with a mean diameter of 20-1,000 nm, which are known to contain various bioactive molecules including proteins, lipids, and nucleic acids. Here, we present EVpedia, which is an integrated database of high-throughput datasets from prokaryotic and eukaryotic extracellular vesicles. EVpedia provides high-throughput datasets of vesicular components (proteins, mRNAs, miRNAs, and lipids) present on prokaryotic, non-mammalian eukaryotic, and mammalian extracellular vesicles. In addition, EVpedia also provides an array of tools, such as the search and browse of vesicular components, Gene Ontology enrichment analysis, network analysis of vesicular proteins and mRNAs, and a comparison of vesicular datasets by ortholog identification. Moreover, publications on extracellular vesicle studies are listed in the database. This free web-based database of EVpedia (http://evpedia.info) might serve as a fundamental repository to stimulate the advancement of extracellular vesicle studies and to elucidate the novel functions of these complex extracellular organelles.