NRAV, a Long Noncoding RNA, Modulates Antiviral Responses through Suppression of Interferon-Stimulated Gene Transcription

SummaryLong noncoding RNAs (lncRNAs) modulate various biological processes, but their role in host antiviral responses is largely unknown. Here we identify a lncRNA as a key regulator of antiviral innate immunity. Following from the observation that a lncRNA that we call negative regulator of antiviral response (NRAV) was dramatically downregulated during infection with several viruses, we ectopically expressed NRAV in human cells or transgenic mice and found that it significantly promotes influenza A virus (IAV) replication and virulence. Conversely, silencing NRAV suppressed IAV replication and virus production, suggesting that reduction of NRAV is part of the host antiviral innate immune response to virus infection. NRAV negatively regulates the initial transcription of multiple critical interferon-stimulated genes (ISGs), including IFITM3 and MxA, by affecting histone modification of these genes. Our results provide evidence for a lncRNA in modulating the antiviral interferon response

Cassava genome from a wild ancestor to cultivated varieties

Cassava is a major tropical food crop in the Euphorbiaceae family that has high carbohydrate production potential and adaptability to diverse environments. Here we present the draft genome sequences of a wild ancestor and a domesticated variety of cassava and comparative analyses with a partial inbred line. We identify 1,584 and 1,678 gene models specific to the wild and domesticated varieties, respectively, and discover high heterozygosity and millions of single-nucleotide variations. Our analyses reveal that genes involved in photosynthesis, starch accumulation and abiotic stresses have been positively selected, whereas those involved in cell wall biosynthesis and secondary metabolism, including cyanogenic glucoside formation, have been negatively selected in the cultivated varieties, reflecting the result of natural selection and domestication. Differences in microRNA genes and retrotransposon regulation could partly explain an increased carbon flux towards starch accumulation and reduced cyanogenic glucoside accumulation in domesticated cassava. These results may contribute to genetic improvement of cassava through better understanding of its biology

A critical role of CDKN3 in Bcr-Abl-mediated tumorigenesis.

CDKN3 (cyclin-dependent kinase inhibitor 3), a dual specificity protein phosphatase, dephosphorylates cyclin-dependent kinases (CDKs) and thus functions as a key negative regulator of cell cycle progression. Deregulation or mutations of CDNK3 have been implicated in various cancers. However, the role of CDKN3 in Bcr-Abl-mediated chronic myelogenous leukemia (CML) remains unknown. Here we found that CDKN3 acts as a tumor suppressor in Bcr-Abl-mediated leukemogenesis. Overexpression of CDKN3 sensitized the K562 leukemic cells to imanitib-induced apoptosis and dramatically inhibited K562 xenografted tumor growth in nude mouse model. Ectopic expression of CDKN3 significantly reduced the efficiency of Bcr-Abl-mediated transformation of FDCP1 cells to growth factor independence. In contrast, depletion of CDKN3 expression conferred resistance to imatinib-induced apoptosis in the leukemic cells and accelerated the growth of xenograph leukemia in mice. In addition, we found that CDKN3 mutant (CDKN3-C140S) devoid of the phosphatase activity failed to affect the K562 leukemic cell survival and xenografted tumor growth, suggesting that the phosphatase of CDKN3 was required for its tumor suppressor function. Furthermore, we observed that overexpression of CDKN3 reduced the leukemic cell survival by dephosphorylating CDK2, thereby inhibiting CDK2-dependent XIAP expression. Moreover, overexpression of CDKN3 delayed G1/S transition in K562 leukemic cells. Our results highlight the importance of CDKN3 in Bcr-Abl-mediated leukemogenesis, and provide new insights into diagnostics and therapeutics of the leukemia

Correction: Suppression of Interferon Lambda Signaling by SOCS-1 Results in Their Excessive Production during Influenza Virus Infection.

[This corrects the article DOI: 10.1371/journal.ppat.1003845.]

Study on nanocellulose by high pressure homogenization in homogeneous isolation

Nanocellulose from cotton cellulose was prepared by high pressure homogenization (HPH) in ionic liquids (1-butyl-3-methylimidazolium chloride ([Bmim]Cl). The nanocellulose possessed narrow particle size distribution, with diameter range of 10–20 nm. Weight average molecular weight (Mw) of nanocellulose treated by HPH was lower (173.8 kDa) than the one ILs treated cellulose (344.6 kDa). X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FT-IR), and Solid-state CP/MAS 13C NMR measurements were employed to study the mechanism of structural changes, which suggested that network structure between cellulose chains were destructed by the shearing forces of HPH in combination with ionic liquids. The intermolecular and intra-molecular hydrogen bonds of cellulose were further destroyed, leading to the long cellulose molecular chains being collapsed into short chains. Therefore, the nanocellulose could provide desired properties, such as lower thermal stability and strong water holding capacity. Results indicated that it had great potential in the applications for packaging, medicines, cosmetics and tissue engineering

Nondestructive in Situ Characterization of Molecular Structures at the Surface and Buried Interface of Silicon-Supported Low‑<i>k</i> Dielectric Films

As low-<i>k</i> dielectric/copper interconnects continue to scale down in size, the interfaces of low-<i>k</i> dielectric materials will increasingly determine the structure and properties of the materials. We report an in situ nondestructive characterization method to characterize the molecular structure at the surface and buried interface of silicon-supported low-<i>k</i> dielectric thin films using interface sensitive infrared-visible sum frequency generation vibrational spectroscopy (SFG). Film thickness-dependent reflected SFG signals were observed, which were explained by multiple reflections of the input and SFG beams within the low-<i>k</i> film. The effect of multiple reflections on the SFG signal was determined by incorporating thin-film interference into the local field factors at the low-<i>k</i>/air and Si/low-<i>k</i> interfaces. Simulated thickness-dependent SFG spectra were then used to deduce the relative contributions of the low-<i>k</i>/air and low-<i>k</i>/Si interfaces to the detected SFG signal. The nonlinear susceptibilities at each interface, which are directly related to the interfacial molecular structure, were then deduced from the isolated interfacial contributions to the detected SFG signal. The method developed here is general and demonstrates that SFG measurements can be integrated into other modern analytical and microfabrication methods that utilize silicon-based substrates. Therefore, the molecular structure at the surface and buried interface of thin polymer or organic films deposited on silicon substrates can be measured in the same experimental geometry used to measure many optical, electrical, and mechanical properties

In Situ Observation of Water Behavior at the Surface and Buried Interface of a Low‑K Dielectric Film

Water adsorption in porous low-k dielectrics has become a significant challenge for both back-end-of-line integration and reliability. A simple method is proposed here to achieve in situ observation of water structure and water-induced structure changes at the poly­(methyl silsesquioxane) (PMSQ) surface and the PMSQ/solid buried interface at the molecular level by combining sum frequency generation (SFG) vibrational spectroscopic and Fourier transform infrared (FTIR) spectroscopic studies. First, in situ SFG investigations of water uptake were performed to provide direct evidence that water diffuses predominantly along the PMSQ/solid interface rather than through the bulk. Furthermore, SFG experiments were conducted at the PMSQ/water interface to simulate water behavior at the pore inner surfaces for porous low-k materials. Water molecules were found to form strong hydrogen bonds at the PMSQ surface, while weak hydrogen bonding was observed in the bulk. However, both strongly and weakly hydrogen bonded water components were detected at the PMSQ/SiO₂ buried interface. This suggests that the water structures at PMSQ/solid buried interfaces are also affected by the nature of solid substrate. Moreover, the orientation of the Si-CH₃ groups at the buried interface was permanently changed by water adsorption, which might due to low flexibility of Si-CH₃ groups at the buried interface. In brief, this study provides direct evidence that water molecules tend to strongly bond (chemisorbed) with low-k dielectric at pore inner surfaces and at the low-k/solid interface of porous low-k dielectrics. Therefore, water components at the surfaces, rather than the bulk, are likely more responsible for chemisorbed water related degradation of the interconnection layer. Although the method developed here was based on a model system study, we believe it should be applicable to a wide variety of low-k materials