SUMMARY Abundantly expressed in fetal tissues and adult muscle, the developmentally regulated H19 long noncoding RNA (lncRNA) has been implicated in human genetic disorders and cancer. However, how H19 acts to regulate gene function has remained enigmatic, despite the recent implication of its encoded miR675 in limiting placental growth. We noted that vertebrate H19 harbors both canonical and noncanonical binding sites for the let-7 family of microRNAs, which plays important roles in development, cancer, and metabolism. Using H19 knockdown and overexpression, combined with in vivo crosslinking and genome-wide transcriptome analysis, we demonstrate that H19 modulates let-7 availability by acting as a molecular sponge. The physiological significance of this interaction is highlighted in culture where H19 depletion causes precocious muscle differentiation, a phenotype recapitulated by let-7 overexpression. Our results reveal an unexpected mode of action of H19 and identify this lncRNA as an important regulator of the major let-7 family of microRNAs.
Aromaticity is a concept invented to account for the unusual stability of an important class of organic molecules: the aromatic compounds. Here we report experimental and theoretical evidence of aromaticity in all-metal systems. A series of bimetallic clusters with chemical composition MAl4- (M = Li, Na, or Cu), was created and studied with photoelectron spectroscopy and ab initio calculations. All the MAl4- species possess a pyramidal structure containing an M+ cation interacting with a square Al4(2-) unit. Ab initio studies indicate that Al4(2-) exhibits characteristics of aromaticity with two delocalized pi electrons (thus following the 4n + 2 electron counting rule) and a square planar structure and maintains its structural and electronic features in all the MAl4- complexes. These findings expand the aromaticity concept into the arena of all-metal species.
A sol−gel process is described to produce phosphoric acid (PA)-doped polybenzimidazole (PBI) films that operate as fuel cell membranes above 150 °C for extended periods of time without the need for feed gas humidification. When solutions of high molecular weight heterocylic polymers such as polybenzimidazoles in polyphosphoric acid (PPA) were cast into films, a transition from solution state to gel state was observed during the hydrolysis of the solvent from PPA (a good solvent for PBI) to PA (a poor solvent for PBI). The resulting membranes retained high levels of phosphoric acid in the gel structure and exhibited high ionic conductivities and stable mechanical properties at elevated temperatures. Preliminary fuel cell tests have demonstrated the feasibility of such PBI membranes from the sol−gel process for operating a fuel cell at temperatures above 150 °C without any feed gas humidification or pressure requirements for more than 1000 h.
In metastatic prostate cancer (PCa) cells, imbalance between cell survival and death signals such as constitutive activation of phosphatidylinositol 3-kinase (PI3K)-Akt and inactivation of apoptosisstimulated kinase (ASK1)-JNK pathways is often detected. Here, we show that DAB2IP protein, often down-regulated in PCa, is a potent growth inhibitor by inducing G 0/G1 cell cycle arrest and is proapoptotic in response to stress. Gain of function study showed that DAB2IP can suppress the PI3K-Akt pathway and enhance ASK1 activation leading to cell apoptosis, whereas loss of DAB2IP expression resulted in PI3K-Akt activation and ASK1-JNK inactivation leading to accelerated PCa growth in vivo. Moreover, glandular epithelia from DAB2IP ؊/؊ animal exhibited hyperplasia and apoptotic defect. Structural functional analyses of DAB2IP protein indicate that both proline-rich (PR) and PERIOD-like (PER) domains, in addition to the critical role of C2 domain in ASK1 activity, are important for modulating PI3K-Akt activity. Thus, DAB2IP is a scaffold protein capable of bridging both survival and death signal molecules, which implies its role in maintaining cell homeostasis.cell apoptosis ͉ prostate cancer ͉ signal transduction
Surface recognition and penetration are among the most critical plant infection processes in foliar pathogens. In Magnaporthe oryzae, the Pmk1 MAP kinase regulates appressorium formation and penetration. Its orthologs also are known to be required for various plant infection processes in other phytopathogenic fungi. Although a number of upstream components of this important pathway have been characterized, the upstream sensors for surface signals have not been well characterized. Pmk1 is orthologous to Kss1 in yeast that functions downstream from Msb2 and Sho1 for filamentous growth. Because of the conserved nature of the Pmk1 and Kss1 pathways and reduced expression of MoMSB2 in the pmk1 mutant, in this study we functionally characterized the MoMSB2 and MoSHO1 genes. Whereas the Momsb2 mutant was significantly reduced in appressorium formation and virulence, the Mosho1 mutant was only slightly reduced. The Mosho1 Momsb2 double mutant rarely formed appressoria on artificial hydrophobic surfaces, had a reduced Pmk1 phosphorylation level, and was nonresponsive to cutin monomers. However, it still formed appressoria and caused rare, restricted lesions on rice leaves. On artificial hydrophilic surfaces, leaf surface waxes and primary alcohols-but not paraffin waxes and alkanes- stimulated appressorium formation in the Mosho1 Momsb2 mutant, but more efficiently in the Momsb2 mutant. Furthermore, expression of a dominant active MST7 allele partially suppressed the defects of the Momsb2 mutant. These results indicate that, besides surface hydrophobicity and cutin monomers, primary alcohols, a major component of epicuticular leaf waxes in grasses, are recognized by M. oryzae as signals for appressorium formation. Our data also suggest that MoMsb2 and MoSho1 may have overlapping functions in recognizing various surface signals for Pmk1 activation and appressorium formation. While MoMsb2 is critical for sensing surface hydrophobicity and cutin monomers, MoSho1 may play a more important role in recognizing rice leaf waxes.
The presence and release of nanoparticles (NPs) into the environment have important implications for human health and the environment. A critical aspect of the risk assessment of nanoparticles is to understand the interactions of manufactured nanoparticles with plants. In this study, the uptake and distribution characteristics of two types of ceria nanoparticles with sizes of ca. 7 nm and 25 nm in cucumber plants were investigated using a radiotracer method and other techniques. With increasing concentration of the nanoparticles, concentration dependent absorption by the plant roots was noticed, but the majority of the particles only loosely adhered to the root surface. The seedlings treated with 7 nm ceria particles showed significantly higher ceria contents in both roots and shoots than those exposed to 25 nm ceria particles at all test concentrations (2, 20, and 200 mg L(-1)). Only very limited amounts of ceria nanoparticles could be transferred from the roots to shoots because the entry of nanoparticles into the roots was difficult. However, the results of tissue distributions of ceria nanoparticles in the plants and two dimensional distributions of the particles in the leaves imply that once they have entered into the vascular cylinder, ceria nanoparticles could move smoothly to the end of the vascular bundle along with water flow. To the best of our knowledge, this is the first detailed study of uptake and distribution of metal oxide nanoparticles in plants.
Helical crystalline silicon carbide nanowires covered with a silicon oxide sheath (SiC/SiO 2 ) have been synthesized by a chemical vapor deposition technique. The SiC core typically has diameters of 10−40 nm with a helical periodicity of 40−80 nm and is covered by a uniform layer of 30−60 nm thick amorphous SiO 2 . A screw-dislocation-driven growth process is proposed for the formation of this novel structure based on detailed structural characterizations. The helical nanostructures may find applications as building blocks in nanomechanical or nanoelectronic devices. The screw-dislocation-induced growth mechanism suggests that similar helical nanostructures of a wide range of materials may be synthesized.
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