Cellular senescence has been viewed as a tumor suppression mechanism and also as a contributor to individual aging. Widespread shortening of 3 ′ untranslated regions (3 ′ UTRs) in messenger RNAs (mRNAs) by alternative polyadenylation (APA) has recently been discovered in cancer cells. However, the role of APA in the process of cellular senescence remains elusive. Here, we found that hundreds of genes in senescent cells tended to use distal poly(A) (pA) sites, leading to a global lengthening of 3 ′ UTRs and reduced gene expression. Genes that harbor longer 3 ′ UTRs in senescent cells were enriched in senescence-related pathways. Rras2, a member of the Ras superfamily that participates in multiple signal transduction pathways, preferred longer 3 ′ UTR usage and exhibited decreased expression in senescent cells. Depletion of Rras2 promoted senescence, while rescue of Rras2 reversed senescence-associated phenotypes. Mechanistically, splicing factor TRA2B bound to a core "AGAA" motif located in the alternative 3 ′ UTR of Rras2, thereby reducing the RRAS2 protein level and causing senescence. Both proximal and distal poly(A) signals showed strong sequence conservation, highlighting the vital role of APA regulation during evolution. Our results revealed APA as a novel mechanism in regulating cellular senescence.

Abstract. We prove two conjectures on weighted complete intersections (cf. [10]) and give the complete classification of threefold weighted complete intersections in weighted projective space that are canonically or anticanonically embedded.

Tween 80 (polysorbate 80) has been used as a reducing agent and protecting agent to prepare stable water-soluble silver nanoparticles on a large scale through a one-pot process, which is simple and environmentally friendly. Silver ions can accelerate the oxidation of Tween 80 and then get reduced in the reaction process. The well-ordered arrays such as ribbon-like silver nanostructures could be obtained by adjusting the reaction conditions. High-resolution transmission electron microscopy confirms that ribbon-like silver nanostructures (approximately 50 nm in length and approximately 2 μm in width) are composed of a large number of silver nanocrystals with a size range of 2 to 3 nm. In addition, negative absorbance around 320 nm in the UV-visible spectra of silver nanoparticles has been observed, probably owing to the instability of nanosized silver colloids.

If X is a smooth complex projective 3-fold with ample canonical divisor K, then the inequality K 3 ≥ 2 3 (2p g − 7) holds, where p g denotes the geometric genus. This inequality is nearly sharp. We also give similar, but more complicated, inequalities for general minimal 3-folds of general type.In what follows, we show that Kobayashi's examples indeed attain the minima of K 3 X , provided X is smooth and K X is ample: Corollary 2. If X is a smooth complex projective 3-fold with ample canonical divisor. Then.When X is not necessarily smooth, we have the following 2000 Mathematics Subject Classification. Primary 14J30

Tunable optical and fluorescent properties of graphene quantum dots (GQDs) by heteroatom doping and surface functionalization provide tremendous advantages for practical applications. One of these notable issues is the construction of stimuli-responsive GQDs which can be used as smart green nonmetal materials in the field of sensor and biotechnology. In this work, N-doped graphene quantum dots (NGQDs) encapsulated by organic species were obtained through hydrothermal method, of which the quantum yield achieved 22.9%, much higher than that of bare NGQDs (1%). Interestingly, it was found that the functionalized NGQDs exhibited a color oscillation in open air and its fluorescence emission can be reversibly switched "on−off" via redox reactions. Meanwhile, the PL emission would be transformed from excitation-independent to excitation-dependent through modifying the surface states of NGQDs. The origin of PL is then studied, emphatically distinguishing the role of different C−N configurations and surface functional groups. The NGQDs of distinct optical and luminescent characteristic can serve as fluorescent sensors for detection of CH 2 O and probes for bioimaging.

Water-soluble Ag-Au bimetallic nanostructures were prepared via co-reduction and seed-mediated growth routes employing poly-(4-styrenesulfonic acid-co-maleic acid) (PSSMA) as both a reductant and a stabilizer. Ag-Au alloy nanoparticles were obtained by the co-reduction of AgNO3 and HAuCl4, while Ag-Au core-shell nanostructures were prepared through seed-mediated growth using PSSMA-Au nanoparticle seeds in a heated AgNO3 solution. The optical properties of the Ag-Au alloy and core-shell nanostructures were studied, and the growth mechanism of the bimetallic nanoparticles was investigated. Plasmon resonance bands in the range 422 to 517 nm were observed for Ag-Au alloy nanoparticles, while two plasmon resonances were found in the Ag-Au core-shell nanostructures. Furthermore, discrete dipole approximation theoretical simulation was used to assess the optical property differences between the Ag-Au alloy and core-shell nanostructures. Composition and morphology studies confirmed that the synthesized materials were Ag-Au bimetallic nanostructures.Electronic supplementary materialThe online version of this article (doi:10.1186/s11671-016-1435-4) contains supplementary material, which is available to authorized users.

Retinal pigment epithelial (RPE) degeneration is potentially involved in the pathogenesis of several retinal degenerative diseases. mTORC1 signaling is shown as a crucial regulator of many biological processes and disease progression. In this study, we aimed at investigating the role of mTORC1 signaling in RPE degeneration. Methods : Western blots were conducted to detect mTORC1 expression pattern during RPE degeneration. Cre-loxP system was used to generate RPE-specific mTORC1 activation mice. Fundus, immunofluorescence staining, transmission electron microscopy, and targeted metabolomic analysis were conducted to determine the effects of mTORC1 activation on RPE degeneration in vivo. Electroretinography, spectral-domain optical coherence tomography, and histological experiments were conducted to determine the effects of mTORC1 activation on choroidal and retinal function in vivo . Results : RPE-specific activation of mTORC1 led to RPE degeneration as shown by the loss of RPE-specific marker, compromised cell junction integrity, and intracellular accumulation of lipid droplets. RPE degeneration further led to abnormal choroidal and retinal function. The inhibition of mTORC1 signaling with rapamycin could partially reverse RPE degeneration. Targeted metabolomics analysis further revealed that mTORC1 activation affected the metabolism of purine, carboxylic acid, and niacin in RPE. Conclusion : This study revealed that abnormal activation of mTORC1 signaling leads to RPE degeneration, which could provide a promising target for the treatment of RPE dysfunction-related diseases.

In this article we present a 3-dimensional analogue of a well-known theorem of Bombieri (Inst Hautes Etudes Sci Publ Math 42:171-219, 1973) which characterizes the bi-canonical birationality of surfaces of general type. Let X be a projective minimal threefold of general type with Q-factorial terminal singularities and the geometric genus p g (X ) ≥ 5. We show that the 4-canonical map ϕ 4 is not birational onto its image if and only if X is birationally fibred by a family C of irreducible curves of geometric genus 2 with K X · C 0 = 1 where C 0 is a general irreducible member in C .