Skeletal muscle cells lacking the retinoblastoma protein display defects in muscle gene expression and accumulate in S and G2 phases of the cell cycle.

Viral oncoproteins that inactivate the retinoblastoma tumor suppressor protein (pRb) family both block skeletal muscle differentiation and promote cell cycle progression. To clarify the dependence of terminal differentiation on the presence of the different pRb-related proteins, we have studied myogenesis using isogenic primary fibroblasts derived from mouse embryos individually deficient for pRb, p107, or p130. When ectopically expressed in fibroblasts lacking pRb, MyoD induces an aberrant skeletal muscle differentiation program characterized by normal expression of early differentiation markers such as myogenin and p21, but attenuated expression of late differentiation markers such as myosin heavy chain (MHC). Similar defects in MHC expression were not observed in cells lacking either p107 or p130, indicating that the defect is specific to the loss of pRb. In contrast to wild-type, p107-deficient, or p130-deficient differentiated myocytes that are permanently withdrawn from the cell cycle, differentiated myocytes lacking pRb accumulate in S and G2 phases and express extremely high levels of cyclins A and B, cyclin-dependent kinase (Cdk2), and Cdc2, but fail to readily proceed to mitosis. Administration of caffeine, an agent that removes inhibitory phosphorylations on inactive Cdc2/cyclin B complexes, specifically induced mitotic catastrophe in pRb-deficient myocytes, consistent with the observation that the majority of pRb-deficient myocytes arrest in S and G2. Together, these findings indicate that pRb is required for the expression of late skeletal muscle differentiation markers and for the inhibition of DNA synthesis, but that a pRb-independent mechanism restricts entry of differentiated myocytes into mitosis

Real inequality in Europe since 1500

Introducing a concept of real, as opposed to nominal, inequality of income or wealth suggests some historical reinterpretations, buttressed by a closer look at consumption by the rich. The purchasing powers of different income classes depend on how relative prices move. Relative prices affected real inequality more strongly in earlier centuries than in the twentieth. Between 1500 and about 1800, staple food and fuels became dearer, while luxury goods, especially servants, became cheaper, greatly widening the inequality of lifestyles. Peace, industrialization, and globalization reversed this inegalitarian price effect in the nineteenth century, at least for England

Two-Level Systems in Evaporated Amorphous Silicon

In $e$-beam evaporated amorphous silicon ($a$-Si), the densities of two-level systems (TLS), $n_{0}$ and $\overline{P}$, determined from specific heat $C$ and internal friction $Q^{-1}$ measurements, respectively, have been shown to vary by over three orders of magnitude. Here we show that $n_{0}$ and $\overline{P}$ are proportional to each other with a constant of proportionality that is consistent with the measurement time dependence proposed by Black and Halperin and does not require the introduction of additional anomalous TLS. However, $n_{0}$ and $\overline{P}$ depend strongly on the atomic density of the film ($n_{\rm Si}$) which depends on both film thickness and growth temperature suggesting that the $a$-Si structure is heterogeneous with nanovoids or other lower density regions forming in a dense amorphous network. A review of literature data shows that this atomic density dependence is not unique to $a$-Si. These findings suggest that TLS are not intrinsic to an amorphous network but require a heterogeneous structure to form

Effects of ethanolic extract of datura stramonium leaves on the histomorphology and biochemical indices of liver and kidney functions in rats

Changes in histomorphology and some indices of liver and kidney functions were studied in rats administered doses of ethanolic extracts of Datura stramonium leaves. Methods: Four experimental groups of rats were respectively given oral doses of 50mg/kg, 100mg/kg and 200mg/kg of the extract daily for six weeks. Rats were sacrificed at the end of the six weeks and blood samples were collected for biochemical analysis. The livers and kidneys of the rates were harvested for histological studies. Results: The results showed that alanine transaminase (ALT) and bilirubin levels were significantly (P<0.05) higher in the groups administered 100mg/kg and 200mg/kg extracts than the control group. The extracts at similar doses also increased significantly (p<0.05) the serum urea and creatinine levels. Histological evaluation of the organs of localization revealed dose-dependent effects of treatment with the extract. Conclusion:The study has shown that Datura stramonium leaf extracts administered with 100 200mg/kg for six weeks caused liver and kidney damages in rats

Prices and Real Inequality in Europe since 1500

Introducing a concept of real, as opposed to nominal, inequality of income or wealth suggests some historical reinterpretations, buttressed by a closer look at consumption by the rich. The purchasing powers of different income classes depend on how relative prices move. The influence of relative prices on real inequality was greater in the sixteenth through nineteenth centuries than in the twentieth. Between 1500 and about 1800, staple food and fuels became dearer, while luxury goods, especially servants, became cheaper, greatly widening the inequality of lifestyles. Peace, industrialization, and globalization reversed this inegalitarian price effect in the nineteenth century

A Framework for the Impact of IT on Organizational Performance

Abstract: Purpose -Despite the constant stream of research investigating information technology (IT) business value, IT capabilities, and competitive advantage, researchers are calling for a more coherent understanding of the firm-level impacts of IT, and how those firm-level impacts can be measured. The purpose of this study is to investigate the multitude of organization-level studies of the impact of IT. Originality/value -The research framework proposed provides a comprehensive snapshot of IS studies on organizational performance. IT business value | organizational impact | productivity rate | profitability | financia

PERP, an apoptosis-associated target of p53, is a novel member of the PMP-22/gas3 family

The p53 tumor suppressor activates either cell cycle arrest or apoptosis in response to cellular stress. Mouse embryo fibroblasts (MEFs) provide a powerful primary cell system to study both p53-dependent pathways. Specifically, in response to DNA damage, MEFs undergo p53-dependent G(1) arrest, whereas MEFs expressing the adenovirus E1A oncoprotein undergo p53-dependent apoptosis. As the p53-dependent apoptosis pathway is not well understood, we sought to identify apoptosis-specific p53 target genes using a subtractive cloning strategy. Here, we describe the characterization of a gene identified in this screen, PERP, which is expressed in a p53-dependent manner and at high levels in apoptotic cells compared with G(1)-arrested cells. PERP induction is linked to p53-dependent apoptosis, including in response to E2F-1-driven hyperproliferation. Furthermore, analysis of the PERP promoter suggests that PERP is directly activated by p53. PERP shows sequence similarity to the PMP-22/gas3 tetraspan membrane protein implicated in hereditary human neuropathies such as Charcot-Marie-Tooth, Like PMP-22/gas3, PERP is a plasma membrane protein, and importantly, its expression causes cell death in fibroblasts. Taken together, these data suggest that PERP is a novel effector of p59-dependent apoptosis