FADD is an adaptor known to transmit apoptotic signals from members of the tumor necrosis factor receptor family. We show here that FADD has a domain implicated in cell proliferation. Mice bearing the Asp mutation in the serine 191 phosphorylation site are runted and anemic and display splenomegaly. Apoptosis is unimpaired in these mice, but they exhibit many immune developmental problems indicative of proliferative defects. Mutant FADD T cells are defective in cell cycle progression, suggesting that regulation of phosphorylation at serine 191 is essential for growth/proliferation. Remarkably, serine 191 is conserved among mammalian FADD proteins, but this C-terminal region is absent in lower organisms, suggesting that FADD acquired a domain during evolution, rendering it a "proliferation-apoptosis coupler" that balances cell proliferation and apoptosis.

We have performed the first single-particle spectroscopic measurements on individual graphene quantum dots (GQDs) and revealed several intriguing fluorescent phenomena that are otherwise hidden in the optical studies of ensemble GQDs. First, despite noticeable differences in the size and the number of layers from particle to particle, all of the GQDs studied possess almost the same spectral lineshapes and peak positions. Second, GQDs with more layers are normally brighter emitters but are associated with shorter fluorescent lifetimes. Third, the fluorescent spectrum of GQDs was red-shifted upon being aged in air, possibly due to the water desorption effect. Finally, the missing emission of single photons and stable fluorescence without any intermittent behavior were observed from individual GQDs.

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Inhibition of protein neddylation, particularly cullin neddylation, has emerged as a promising anticancer strategy, as evidenced by the antitumor activity in preclinical studies of the Nedd8-activating enzyme (NAE) inhibitor MLN4924. This small molecule can block the protein neddylation pathway and is now in clinical trials. We and others have previously shown that the antitumor activity of MLN4924 is mediated by its ability to induce apoptosis, autophagy and senescence in a cell context-dependent manner. However, whether MLN4924 has any effect on tumor angiogenesis remains unexplored. Here we report that MLN4924 inhibits angiogenesis in various in vitro and in vivo models, leading to the suppression of tumor growth and metastasis in highly malignant pancreatic cancer, indicating that blockage of angiogenesis is yet another mechanism contributing to its antitumor activity. At the molecular level, MLN4924 inhibits Cullin–RING E3 ligases (CRLs) by cullin deneddylation, causing accumulation of RhoA at an early stage to impair angiogenic activity of vascular endothelial cells and subsequently DNA damage response, cell cycle arrest and apoptosis due to accumulation of other tumor-suppressive substrates of CRLs. Furthermore, we showed that inactivation of CRLs, via small interfering RNA (siRNA) silencing of its essential subunit ROC1/RBX1, recapitulates the antiangiogenic effect of MLN4924. Taken together, our study demonstrates a previously unrecognized role of neddylation in the regulation of tumor angiogenesis using both pharmaceutical and genetic approaches, and provides proof of concept evidence for future development of neddylation inhibitors (such as MLN4924) as a novel class of antiangiogenic agents.

Upconversion (UC) based luminescent materials have promising applications in noncontact temperature sensors. How to improve the sensitivity is one main object at present. This work presented several strategies for optical temperature sensing based on UC spectra of the YWO:Yb-Er/Ho/Tm phosphors. The improvement for the relative ( S) and absolute ( S) sensitivities were discussed by using a fluorescence intensity ratio technique. It includes thermally coupled levels (TCLs) and non-TCLs. It was proposed that a piecewise expression could be employed to achieve high S value for TCLs. However, improving the S value is limited for TCLs. With regard to the non-TCLs, S and S are not restricted, but not easy to be improved synchronously. On the other hand, the morphology and UC spectra of the samples were also studied. The above investigation could be instructive to develop new luminescent materials with high sensitivity.

The development of technology for the synthesis of metals and alloys continues to be one of the most important challenges in materials science. A general method for the synthesis of metals is to reduce metal oxides with hydrogen or carbon at high temperature. Pure metals are then used as starting materials to synthesize alloys by a melting method. There are some existing methods used to synthesize metals and alloys that have improvement of their capabilities. [1][2][3] However, the reduction of energy costs in the synthesis process is one of the critical factors for making the overall products cost-effective. Autocombustion is a self-sustaining method for heat generation from its own exothermic reaction. [4,5] In addition, the sol-gel technique has been widely used for the synthesis of a variety of metal oxides by mixing of different elements at the atomic level. [6][7][8][9][10][11][12][13] Herein, we describe a versatile new strategy for producing pure metals and alloys by combining the sol-gel method and autocombustion; similar methods have been successfully used for the synthesis of metal oxides. [14,15] We used metal nitrate, citric acid, and ammonia as starting materials; the dried gels were prepared through a routine sol-gel approach. The autocombustion was activated at 300 8C in a tube furnace. The resulting materials were characterized by X-ray diffraction (XRD) with Cu Ka radiation. This method has the following features: 1) simple apparatus with inexpensive raw materials; 2) a relatively simple synthesis process with fine and highly homogeneous powder products; and 3) a very low temperature is required to activate the reaction, and importantly the combustion can then continue without extra energy supply.Pure metals are important materials that are extensively used for their unique properties (such as magnetic, catalytic, superconducting). Furthermore, atoms of pure metals can be used as building blocks in the construction of different kinds of alloys. As shown in Figure 1, pure Co, Ni, Cu, Ag, and Bi were identified. The morphologies of the synthesized metals were characterized by transmission electron microscopy (TEM), which showed that the metals and alloys were composed of nanoparticles of size from several nanometers to 100 nm. (111) plane in nickel. From this image it is estimated that the grain size of nickel is about 10 nm. TEM images of the metals Co, Cu, Ag, and Bi and Co 0.5 Ni 0.5 alloy can be found in the Supporting Information.In addition to the synthesis of pure metals, we have demonstrated the successful synthesis of a series of Co x Ni 1Àx (x = 0.2, 0.4, 0.5, 0.6) alloys. The XRD pattern of Co 0.5 Ni 0.5 is shown in Figure 1 (see the Supporting Information for other XRD patterns). The (111) peak shifts to a higher angle with an increase of the ratio of the Ni atom. As the crystalline unit

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The end-Permian extinction is typically ascribed to massive volcanic eruptions, but direct geochemical evidence linking the two independent events is generally lacking. Zinc is an important micronutrient of marine phytoplanktons, and Zn isotope (d 66 Zn) ratios of seawater are markedly higher than those of volcanic rocks and riverine waters. We conducted high-resolution Zn concentration and Zn isotope analyses on carbonate rocks across the Permian-Triassic boundary (PTB) in the Meishan section of south China. An abrupt increase of Zn concentration and a concomitant 0.5‰ decrease in d 66 Zn occur ~35 k.y. before the mass extinction and carbon isotope (d 13 C) minima. Mass balance calculation demonstrates that a 0.5‰ negative shift in d 66 Zn within thousands of years requires rapid and massive input of isotopically light Zn from volcanic ashes, hydrothermal inputs, and/or extremely fast weathering of large igneous provinces. A positive d 66 Zn shift of as much as 1.0‰ following the mass extinction demonstrates that primary productivity recovered and reached a maximum in fewer than 360 k.y. Our finding provides insights into the marine Zn cycling across the PTB and clarifies the temporal relationship and duration of events, including intensive volcanism, carbon isotope excursion, mass extinction, and widespread ocean anoxia.