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Parkinson's disease (PD) and Alzheimer's disease exhibit common features of neurodegenerative diseases and can be caused by numerous factors. A common feature of these diseases is neurotoxic inflammation by activated microglia, indicating that regulation of microglial activation is a potential mechanism for preserving neurons in the adult brain. Recently, we reported that upregulation of prothrombin kringle-2 (pKr-2), one of the domains that make up prothrombin and which is cleaved and generated by active thrombin, induces nigral dopaminergic (DA) neuronal death through neurotoxic microglial activation in the adult brain. In this study, we show that silibinin, a flavonoid found in milk thistle, can suppress the production of inducible nitric oxide synthase and neurotoxic inflammatory cytokines, such as interleukin-1β and tumor necrosis factor-α, after pKr-2 treatment by downregulating the extracellular signal-regulated kinase signaling pathway in the mouse substantia nigra. Moreover, as demonstrated by immunohistochemical staining, measurements of the dopamine and metabolite levels, and open-field behavioral tests, silibinin treatment protected the nigrostriatal DA system resulting from the occurrence of pKr-2-triggered neurotoxic inflammation in vivo. Thus, we conclude that silibinin may be beneficial as a natural compound with anti-inflammatory effects against pKr-2-triggered neurotoxicity to protect the nigrostriatal DA pathway and its properties, and thus, may be applicable for PD therapy.

The synthesis of indazoles from pyrazoles and internal alkynes is described. Instead of complex benzenoid compounds, readily available pyrazoles were used for the preparation of indazoles by reaction of the C-H bonds of the heterocyclic ring. Oxidative benzannulation was also applied to imidazoles, providing benzimidazoles. This convergent strategy enabled alteration of the photochemical properties of benzo-fused diazoles by varying the substituents at the benzene ring, thus leading to the development of tetraarylindazoles as new fluorophores.

Pd-catalyzed C–H annulation reactions of halo- and aryl-heteroarenes were developed using readily available o-bromobiaryls and o-dibromoaryls, respectively. A variety of five-membered heteroarenes rapidly provided the corresponding phenanthrene-fused heteroarenes, which led to the identification of phenanthro-pyrazole and thiazole as new, stable −2 V redox couples. The flexible syntheses and tunability of the redox potentials of these azole-fused phenanthrenes over a wide range are expected to facilitate their application as redox-active organic functional materials.

A simple method was reported to fabricate self-cleaning and water–oil separation fabrics sprayed with hot-iron-treated graphene oxide (GO). The GO solution was prepared with a modified Hummers' method and coated on the fabrics by spraying or soaking method. A 160 °C hot iron was pressed at the surface of the fabrics to make it flat, dry, thermally reduced in part, and strongly bonded. Afterward, the fabrics were thermally reduced at 250 °C for 20 minutes in an oven. The reduced graphene oxide (rGO) coated fabrics exhibited a superhydrophobic nature with a water contact angle of 129.4°, through which water could barely permeate the fabrics, in contrast to oil and organic solvents of low polarity. Additionally, this rGO fabric presented outstanding mechanical properties as well as a reusable stability.

Ras homolog enriched in brain (Rheb) regulates diverse cellular functions by modulating its nucleotide-bound status. Although Rheb contains a high basal GTP level, the regulatory mechanism of Rheb is not well understood. In this study, we propose soluble αβ-tubulin acts as a constitutively active Rheb activator, which may explain the reason why Rheb has a high basal GTP levels. We found that soluble αβ-tubulin is a direct Rheb-binding protein and that its deacetylated form has a high binding affinity for Rheb. Modulation of both soluble and acetylated αβ-tubulin levels affects the level of GTP-bound Rheb. This occurs in the mitotic phase in which the level of acetylated αβ-tubulin is increased but that of GTP-bound Rheb is decreased. Constitutively active Rheb-overexpressing cells showed an abnormal mitotic progression, suggesting the deacetylated αβ-tubulin-mediated regulation of Rheb status may be important for proper mitotic progression. Taken together, we propose that deacetylated soluble αβ-tubulin is a novel type of positive regulator of Rheb and may play a role as a temporal regulator for Rheb during the cell cycle.

We report ambivalent rejection behavior of a graphene oxide membrane (GOM) having a reduced interlayer spacing. Ultrathin GOMs having a thickness of 50 nm were fabricated using a vacuum filtration method followed by subjecting the samples to thermal reduction at 162 °C. The interlayer spacing of GOMs was reduced by 1 A on thermal reduction as compared with that of the natural GOMs. The rejection rate with dye molecules was tested using dyes having three different types of charges in a dead-end filtration instrument. Rejection rate of the reduced GOM with the dyes having an opposite charge was improved up to 99.7%, indicating the dominant effect of the physical sieving diameter. In contrast, in the case of ion permeation of natural GOM, a higher rejection rate for several metal ions was observed as compared with that of GOMs having 1 A smaller interlayer spacing, indicating the dominant effect of surface charges on the GOM samples.

NHERF1/EBP50 (Na+/H+ exchanger regulating factor 1; Ezrin-binding phosphoprotein of 50 kDa) organizes stable protein complexes beneath the apical membrane of polar epithelial cells. By contrast, in cancer cells without any fixed polarity, NHERF1 often localizes in the cytoplasm. The regulation of cytoplasmic NHERF1 and its role in cancer progression remain unclear. In this study, we found that, upon lysophosphatidic acid (LPA) stimulation, cytoplasmic NHERF1 rapidly translocated to the plasma membrane, and subsequently to cortical protrusion structures, of ovarian cancer cells. This movement depended on direct binding of NHERF1 to C-terminally phosphorylated ERM proteins (cpERMs). Moreover, NHERF1 depletion downregulated cpERMs and further impaired cpERM-dependent remodeling of the cell cortex, suggesting reciprocal regulation between these proteins. The LPA-induced protein complex was highly enriched in migratory pseudopodia, whose formation was impaired by overexpression of NHERF1 truncation mutants. Consistent with this, NHERF1 depletion in various types of cancer cells abolished chemotactic cell migration toward a LPA gradient. Taken together, our findings suggest that the high dynamics of cytosolic NHERF1 provide cancer cells with a means of controlling chemotactic migration. This capacity is likely to be essential for ovarian cancer progression in tumor microenvironments containing LPA.

Phospholipases (PLC, PLD and PLA) are essential mediators of intracellular and intercellular signalling. They can function as phospholipid-hydrolysing enzymes that can generate many bioactive lipid mediators, such as diacylglycerol, phosphatidic acid, lysophosphatidic acid and arachidonic acid. Lipid mediators generated by phospholipases regulate multiple cellular processes that can promote tumorigenesis, including proliferation, migration, invasion and angiogenesis. Although many individual phospholipases have been extensively studied, how phospholipases regulate diverse cancer-associated cellular processes and the interplay between different phospholipases have yet to be fully elucidated. A thorough understanding of the cancer-associated signalling networks of phospholipases is necessary to determine whether these enzymes can be targeted therapeutically.

Recently, the lack of clean and safe drinking water is huge challenge because of rapid population growth, severe droughts and environmental pollution. Two-dimensional Graphene oxide (GO) membrane with their ultrafast permanence, outstanding mechanical properties, high chemical stability is increasingly emerging as promising candidate for water purification process. But GO-based water purification technology still needs further investigation and optimization. Here, we fabricated ultrathin graphene oxide membrane by the vacuum filtration method, and successfully applied for the water purification. GO membranes with several tenth nm thickness prepared show well stacked layer structure, as characterized by atomic force microscopy and scanning electron microscopy. We have tried pressure-driven filtration to examine water flux, retention and rejection ability of the GO membranes in water purification process. The ultrathin graphene oxide membrane showed high retention and rejection rates for the charged dyes and moderate results for noncharged organic dye.

Phospholipase D (PLD) is a phospholipid-hydrolyzing enzyme that generates phosphatidic acid (PA) as a lipid second messenger by hydrolyzing phosphatidyl choline (PC). Various extracellular signals have been reported to activate PLD, which acts as a key mediator of many cellular functions through the generation of PA and the interactions of PLD and PA with their binding partners. Currently, about 60 PLD-binding partners, including proteins and phospholipids, are known, and PA has been found to interact with about 50 proteins. Although the interactions of binding molecules with PLD and PA are complex and multilayered, the unique interactions between them are important for their unique intracellular functions. Here, we address the interrelationships between PLD and PA and their binding partners in several key signaling pathways, such as the EGFR–ERK signaling axis, nutrient/growth signaling axis, and cytoskeletal reorganization machinery axis. These interrelationships demonstrate dynamic interactions and cooperative regulation, which mediate special intracellular functions. Furthermore, we describe the regulation and functions of PLD in mediating normal and pathological signaling. Additionally, we summarize the roles of PLD as determined in animal studies (Drosophila, zebrafish, and mice) and changes in the PLD expression level in disease states. These findings provide new insight into the functions of PLD under pathophysiological conditions.

Phospholipase D (PLD) is a phosphatidyl choline (PC)-hydrolyzing enzyme that generates phosphatidic acid (PA), a lipid second messenger that modulates diverse intracellular signaling. Through interactions with signaling molecules, both PLD and PA can mediate a variety of cellular functions, such as, growth/proliferation, vesicle trafficking, cytoskeleton modulation, development, and morphogenesis. Therefore, systemic approaches for investigating PLD networks including interrelationship between PLD and PA and theirs binding partners, such as proteins and lipids, can enhance fundamental knowledge of roles of PLD and PA in diverse biological processes. In this review, we summarize previously reported protein-protein and protein-lipid interactions of PLD and PA and their binding partners. In addition, we describe the functional roles played by PLD and PA in these interactions, and provide PLD network that summarizes these interactions. The PLD network suggests that PLD and PA could act as a decision maker and/or as a coordinator of signal dynamics. This viewpoint provides a turning point for understanding the roles of PLD-PA as a dynamic signaling hub.