Quiescence versus apoptosis: Myc abundance determines pathway of exit from the cell cycle

When exposed to diverse growth conditions in vitro, cells can respond by entering states of proliferation, quiescence, differentiation or apoptosis. While the choices among these states can be influenced by proto-oncogene expression, how these disparate outcomes are achieved remains poorly understood. To address these issues, we have generated rodent fibroblast cell lines that harbor a human c-myc gene under the control of a tetracycline-regulated promoter. When Myc-induced cells are deprived of serum growth factors, they rapidly become apoptotic with the onset of apoptosis preceded by a large, transient increase in cdk2 kinase activity that is associated with the induction of cdc25A phosphatase and the later accumulation of p27Kip1 kinase inhibitor. Surprisingly, serum starvation in the absence of myc overexpression, (which leads to quiescence instead of apoptosis) also causes a marked transient elevation in cdk2 kinase activity, an induction of cdc25A and a delayed increase in p27Kip1. Transient elevations in cdk2 kinase activity and cdc25A abundance are required for cell cycle progression, but it is evident that these changes also precede entry to either apoptosis or quiescence in serum-starved cells. These findings suggest that the pathways to both quiescence and apoptosis share regulatory machinery with cell cycle control mechanisms. In addition, the abundance of Myc protein can be critical in the choices among these cellular states.     

Aromatic Linkers Unleash the Antiproliferative Potential of 3-Chloropiperidines Against Pancreatic Cancer Cells

In this study, we describe the synthesis and biological evaluation of a set of bis-3-chloropiperidines (B−CePs) containing rigid aromatic linker structures. A modification of the synthetic strategy also enabled the synthesis of a pilot tris-3-chloropiperidine (Tri-CeP) bearing three reactive meta-chloropiperidine moieties on the aromatic scaffold. A structure–reactivity relationship analysis of B−CePs suggests that the arrangement of the reactive units affects the DNA alkylating activity, while also revealing correlations between the electron density of the aromatic system and the reactivity with biologically relevant nucleophiles, both on isolated DNA and in cancer cells. Interestingly, all aromatic 3-chloropiperidines exhibited a marked cytotoxicity and tropism for 2D and 3D cultures of pancreatic cancer cells. Therefore, the new aromatic 3-chloropiperidines appear to be promising contenders for further development of mustard-based anticancer agents aimed at pancreatic cancers.     

Simulation and measurement of quasi-optical multipliers

The lumped-element finite-difference time-domain method is used to analyze quasi-optical multipliers based on diode loaded slot antennas. The method is validated firstly for a passive microstrip-fed structure then for the diode loaded case in both small- and large-signal regimes. The diode model is separately validated using a series diode mounted on a microstrip line. Input return loss and radiation patterns show good agreement with measurements and the concept of effective conversion loss is introduced and results show reasonable agreement between measurement and simulation. A new diode arrangement is introduced where dual offset diodes are placed in the slot instead of the conventional central diode. The diode position can then act as an extra design parameter. The performance of the two structures has been compared; currently best performance is still obtained for the central-diode structure. Finally, a fully quasi-optical structure is simulated with plane-wave excitation. Central and dual-diode structures are again compared and the diode position and input plane-wave field strengths are optimized. Slot voltage distributions, radiation patterns, and effective quasi-optical conversion losses are presented     

色母液及添加剂的连续混合和计量

概论塑料加工行业中,许多情况下都要使用色料或添加剂。有色的聚合物常用于生产加工薄膜、管材、型材等,当然也可以用于长丝的生产。很常见的生产方法是使用色母粒,一般是在挤出机前的料仓处使用重力添加系统,将色母粒与     

A novel candidate tumor suppressor, ING1, is involved in the regulation of apoptosis

We have recently cloned a novel growth inhibitor and candidate tumor suppressor called p33ING1 (I. Garkavtsev et al., Nature Genet., 14: 415-420, 1996). Because some tumor suppressors participate in the regulation of apoptosis, we hypothesized that the ING1 gene may also play a role in this process. Our results show that p33ING1 levels increase upon the induction of apoptosis in P19 teratocarcinoma cells by serum deprivation. Elevated expression of ING1 in P19 and rodent fibroblast cells containing a tetracycline-controlled human c-myc gene enhanced the extent of serum starvation-induced apoptosis. This suggests that the pathway by which ING1 modulates cell death is synergistic with Myc-dependent apoptosis. Conversely, constitutive expression of an antisense construct of INGI conferred protection against apoptosis in these cells. These data support the idea that loss of proper ING1 function may facilitate tumorigenesis, in part, by reducing the cell's sensitivity to apoptosis.