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 In contrast to wild-type, p107-deficient, or p130-deficient differentiated myocytes that are permanently withdrawn from the cell cycle, differentiated myocytes lacking pRb accumulate in S and G2 phases and express extremely high levels of cyclins A and B, cyclin-dependent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

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

The multifaceted role of regulatory T cells in breast cancer

The microenvironment of breast cancer hosts a dynamic cross talk between diverse players of the immune system. While cytotoxic immune cells are equipped to control tumor growth and metastasis, tumor-corrupted immunosuppressive immune cells strive to impair effective immunity and promote tumor progression. Of these, regulatory T cells (Tregs), the gatekeepers of immune homeostasis, emerge as multifaceted players involved in breast cancer. Intriguingly, clinical observations suggest that blood and intratumoral Tregs can have strong prognostic value, dictated by breast cancer subtype. Accordingly, emerging preclinical evidence shows that Tregs occupy a central role in breast cancer initiation and progression and provide critical support to metastasis formation. Here, Tregs are not only important for immune escape but also promote tumor progression independent of their immune regulatory capacity. Combining insights into Treg biology with advances made across the rapidly growing field of immuno-oncology is expected to set the stage for the design of more effective immunotherapy strategies