Effects of Pyruvate Kinase M2 (PKM2) Gene Deletion on Astrocyte-Specific Glycolysis and Global Cerebral Ischemia-Induced Neuronal Death.

Ischemic stroke is caused by insufficient blood flow to the brain. Astrocytes have a role in bidirectionally converting pyruvate, generated via glycolysis, into lactate and then supplying it to neurons through astrocyte-neuron lactate shuttle (ANLS). Pyruvate kinase M2 (PKM2) is an enzyme that dephosphorylates phosphoenolpyruvate to pyruvate during glycolysis in astrocytes. We hypothesized that a reduction in lactate supply in astrocyte PKM2 gene deletion exacerbates neuronal death. Mice harboring a PKM2 gene deletion were established by administering tamoxifen to Aldh1l1-CreERT2; PKM2f/f mice. Upon development of global cerebral ischemia, mice were immediately injected with sodium l-lactate (250 mg/kg, i.p.). To verify our hypothesis, we compared oxidative damage, microtubule disruption, ANLS disruption, and neuronal death between the gene deletion and control subjects. We observed that PKM2 gene deletion increases the degree of neuronal damage and impairment of lactate metabolism in the hippocampal region after GCI. The lactate administration groups showed significantly reduced neuronal death and increases in neuron survival and cognitive function. We found that lactate supply via the ANLS in astrocytes plays a crucial role in maintaining energy metabolism in neurons. Lactate administration may have potential as a therapeutic tool to prevent neuronal damage following ischemic stroke.

Valid design and evaluation of cathode and anode materials of aqueous zinc ion batteries with high-rate capability and cycle stability.

Although non-aqueous lithium-ion batteries have a high gravimetric density, aqueous zinc-ion batteries (ZIBs) have recently been in the spotlight as an alternative, because ZIBs have characteristics such as high volumetric density, high ionic conductivity, eco-friendliness, low cost, and high safety. However, the improvement in electrochemical performance is limited due to insufficient rate capability and severe cycle fading of the vanadium-oxide-based cathode and zinc-metal-based anode material, which are frequently used as active materials for ZIBs. In addition, complex methods are required to prepare high-performance cathode and anode materials. Therefore, a simple yet effective strategy is needed to obtain high-performance anodes and cathodes. Herein, an ammonium vanadate nanofiber (AVNF) intercalated with NH4+ and H2O as a cathode material for ZIBs was synthesized within 30 minutes through a facile sonochemical method. In addition, an effective Al2O3 layer of 9.9 nm was coated on the surface of zinc foil through an atomic layer deposition technique. As a result, AVNF//60Al2O3@Zn batteries showed a high rate capability of 108 mA h g-1 even at 20 A g-1, and exhibited ultra-high cycle stability with a capacity retention of 94% even after 5000 cycles at a current density of 10 A g-1.

Structural Characterization and Comparison of Monovalent Cation-Exchanged Zeolite-W.

We report comparative structural changes of potassium-contained zeolite-W (K-MER, structural analogue of natural zeolite merlinoite) and monovalent extra-framework cation (EFC)-exchanged M-MERs (M = Li+, Na+, Ag+, and Rb+). High-resolution synchrotron X-ray powder diffraction study precisely determines that crystal symmetry of MERs is tetragonal (I4/mmm). Rietveld refinement results reveal that frameworks of all MERs are geometrically composed of disordered Al/Si tetrahedra, bridged by linkage oxygen atoms. We observe a structural relationship between a group of Li-, Na-, and Ag-MER and the group of K- and Rb-MER by EFC radius and position of M(1) site inside double 8-membered ring unit (d8r). In the former group, a-axes decrease reciprocally, c-axes gradually extend by EFC size, and M(1) cations are located at the middle of the d8r. In the latter group, a- and c-axes lengths become longer and shorter, respectively, than axes of the former group, and these axial changes come from middle-to-edge migration of M(1) cations inside the d8r channel. Unit cell volumes of the Na-, Ag-, and K-MER are ca. 2005 Å3, and the volume expansion in the MER series is limited by EFC size, the number of water molecules, and the distribution of extra-framework species inside the MER channel. EFC sites of M(1) and M(2) show disordered and ordered distribution in the former group, and all EFC sites change to disordered distribution after migration of the M(1) site in the latter group. The amount of water molecules and porosities are inversely proportional to EFC size due to the limitation of volume expansion of MERs. The channel opening area of a pau composite building unit and the amount of water molecules are universally related as a function of cation size because water molecules are mainly distributed inside a pau channel.

NFATC3-PLA2G15 Fusion Transcript Identified by RNA Sequencing Promotes Tumor Invasion and Proliferation in Colorectal Cancer Cell Lines.

PURPOSE: This study was designed to identify novel fusion transcripts (FTs) and their functional significance in colorectal cancer (CRC) lines. MATERIALS AND METHODS: We performed paired-end RNA sequencing of 28 CRC cell lines. FT candidates were identified using TopHat-fusion, ChimeraScan, and FusionMap tools and further experimental validation was conducted through reverse transcription-polymerase chain reaction and Sanger sequencing. FT was depleted in human CRC line and the effects on cell proliferation, cell migration, and cell invasion were analyzed. RESULTS: One thousand three hundred eighty FT candidates were detected through bioinformatics filtering. We selected six candidate FTs, including four inter-chromosomal and two intrachromosomal FTs and each FT was found in at least one of the 28 cell lines. Moreover, when we tested 19 pairs of CRC tumor and adjacent normal tissue samples, NFATC3-PLA2G15 FT was found in two. Knockdown of NFATC3-PLA2G15 using siRNA reduced mRNA expression of epithelial-mesenchymal transition (EMT) markers such as vimentin, twist, and fibronectin and increased mesenchymal-epithelial transition markers of E-cadherin, claudin-1, and FOXC2 in colo-320 cell line harboring NFATC3-PLA2G15 FT. The NFATC3-PLA2G15 knockdown also inhibited invasion, colony formation capacity, and cell proliferation. CONCLUSION: These results suggest that that NFATC3-PLA2G15 FTs may contribute to tumor progression by enhancing invasion by EMT and proliferation.

Identification of Diverse Adenosine-to-Inosine RNA Editing Subtypes in Colorectal Cancer.

PURPOSE: RNA editing generates protein diversity by altering RNA sequences in coding regions without changing the overall DNA sequence. Adenosine-to-inosine (A-to-I) RNA editing events have recently been reported in some types of cancer, but they are rare in human colorectal cancer (CRC). Therefore, this study was conducted to identify diverse RNA editing in CRC. MATERIALS AND METHODS: We compared transcriptome data of 39 CRC samples and paired adjacent tissues from The Cancer Genome Atlas database to identify RNA editing patterns in CRC, focusing on canonical A-to-I RNA edits in coding sequence regions. We investigated nonsynonymous RNA editing patterns by comparing tumor and normal tissue transcriptome data. RESULTS: The number of RNA edits varied from 12 to 42 per sample. We also observed that hypoand hyper-RNA editing patterns were distinguishable within the samples. We found 10 recurrent nonsynonymous RNA editing candidates in nine genes (PDLIM, NEIL1, SRP9, GLI1, APMAP, IGFBP7, ZNF358, COPA, and ZNF587B) and validated some by Sanger sequencing and the inosine chemical erasing assay. We further showed that editing at these positions was performed by the adenosine deaminase acting on RNA 1 enzyme. Most of these genes are hypoedited in CRC, but editing of GLI1 was increased in cancer tissues compared with normal tissues. CONCLUSION: Our results show that nonsynonymous RNA editing patterns can be used to identify CRC patients and could serve as novel biomarkers for CRC.

Identification of long-range epigenetic silencing on chromosome 15q25 and its clinical implication in gastric cancer.

Recent genome-wide epigenomic and transcription profiling studies have demonstrated that epigenetic silencing can encompass multiple neighboring genes, termed as long-range epigenetic silencing (LRES). Herein, we identified a novel LRES region by comparing gene expression of human colon cancer HCT116 cells with their DNA methyltransferase 1 and DNA methyltransferase 3B double-knockout derivative double-knockout cells. Ten consecutive genes spanning 3 Mb of chromosome 15q25 were coordinately silenced, with eight genes showing promoter CpG island hypermethylation and enrichment of repressive histone marks, which were evaluated by bisulfite sequencing analysis and chromatin immunoprecipitation assay. Comparison of primary gastric tumor specimens with normal tissue confirmed that the long-range silencing of this region was tumor specific. Methylation of genes within the LRES region was evaluated in 190 gastric tumor tissues using the MethyLight assay, and their association with clinicopathological features, such as older age, high-grade differentiation, and diffuse or mixed-type histology, was determined. LRES-positive gastric cancer patients (six or more methylated genes) showed lower recurrence and better survival. Our findings emphasize the differential dynamics of DNA methylation and histone modification, indicating the importance of studying the relationship of each epigenetic modification in the context of chromatin domains. Patients with LRES showed lower recurrence and better prognosis, indicating that stratifying patients according to underlying molecular features, such as LRES regions, may better predict recurrence and survival.

On carbon dioxide storage based on biomineralization strategies.

This study focuses on the separation and storage of the global warming greenhouse gas CO(2), and the use of natural biocatalysts in the development of technologies to improve CO(2) storage rates and provide new methods for CO(2) capture. Carbonic anhydrase (CA) has recently been used as a biocatalyst to sequester CO(2) through the conversion of CO(2) to HCO(-) in the mineralization of CaCO(3). Biomimetic CaCO(3) mineralization for carbon capture and storage offers potential as a stable CO(2) capture technology. In this report, we review recent developments in this field and assess disadvantages and improvements in the use of CA in industrial applications. We discuss the contribution that understanding of mechanisms of CO(2) conversion to CO(3)(-) in the formation and regeneration of bivalve shells will make to developments in biomimetic CO(2) storage.