Macropinocytosis confers resistance to therapies targeting cancer anabolism.

Macropinocytic cancer cells scavenge amino acids from extracellular proteins. Here, we show that consuming necrotic cell debris via macropinocytosis (necrocytosis) offers additional anabolic benefits. A click chemistry-based flux assay reveals that necrocytosis provides not only amino acids, but sugars, fatty acids and nucleotides for biosynthesis, conferring resistance to therapies targeting anabolic pathways. Indeed, necrotic cell debris allow macropinocytic breast and prostate cancer cells to proliferate, despite fatty acid synthase inhibition. Standard therapies such as gemcitabine, 5-fluorouracil (5-FU), doxorubicin and gamma-irradiation directly or indirectly target nucleotide biosynthesis, creating stress that is relieved by scavenged nucleotides. Strikingly, necrotic debris also render macropinocytic, but not non-macropinocytic, pancreas and breast cancer cells resistant to these treatments. Selective, genetic inhibition of macropinocytosis confirms that necrocytosis both supports tumor growth and limits the effectiveness of 5-FU in vivo. Therefore, this study establishes necrocytosis as a mechanism for drug resistance

Asymmetric diffusion at the interfaces in multilayers

Nanoscale diffusion at the interfaces in multilayers plays a vital role in controlling their physical properties for a variety of applications. In the present work depth-dependent interdiffusion in a Si/Fe/Si trilayer has been studied with sub-nanometer depth resolution, using x ray standing waves. High depth-selectivity of the present technique allows one to measure diffusion at the two interfaces of Fe namely, Fe-on-Si and Si-on-Fe, independently, yielding an intriguing result that Fe diffusivity at the two interfaces is not symmetric. It is faster at the Fe-on-Si interface. While the values of activation energy at the two interfaces are comparable, the main difference is found in the pre-exponent factor suggesting different mechanisms of diffusion at the two interfaces. This apparently counter-intuitive result has been understood in terms of an asymmetric structure of the interfaces as revealed by depth selective conversion electron Mossbauer spectroscopy. A difference in the surface free energies of Fe and Si can lead to such differences in the structure of the two interfaces.Comment: 4 pages, 5 figure

Length sensing and control for Einstein Telescope Low Frequency

In this paper we describe a feasible length sensing and control scheme for the low frequency interferometers of the Einstein Telescope (ET-LF) along with the techniques used to optimise several optical parameters, including the length of the recycling cavities and the modulation frequencies, using two numerical interferometer simulation packages: Optickle and Finesse. The investigations have suggested the use of certain combinations of sidebands to obtain independent information about the different degrees of freedom

Morphological and Biochemical Analysis of Cicer arietinum L. under Paper Industrial Effluent Stress conditions

To study the effect of paper industrial effluent on chickpea (Cicer arietinum L.) along with different concentration (10%, 20% 40%, 60% 80% and 100%) and pure tape water as a control to compare the effect of paper industrial effluent for 7 days. Physico-chemical characteristics of paper effluent were analyzed in terms of pH, colour, order temperature, DO, BOD, COD, Total hardness, carbonated hardness. All the parameters were found to be higher than the WHO prescribed discharge limits for effluent. The amount of carbohydrate, protein and reducing sugar were comparable with control, their amount were increased at 40% in effluent treated seeds. The chlorophyll content was increased simultaneously with effluent concentration. From this study it is clear that the industrial effluent rich in organic matter and plant nutrients are finding their use in agriculture as cheaper way of disposal