Human embryonic stem cells: preclinical perspectives

Human embryonic stem cells (hESCs) have been extensively discussed in public and scientific communities for their potential in treating diseases and injuries. However, not much has been achieved in turning them into safe therapeutic agents. The hurdles in transforming hESCs to therapies start right with the way these cells are derived and maintained in the laboratory, and goes up-to clinical complications related to need for patient specific cell lines, gender specific aspects, age of the cells, and several post transplantation uncertainties. The different types of cells derived through directed differentiation of hESC and used successfully in animal disease and injury models are described briefly. This review gives a brief outlook on the present and the future of hESC based therapies, and talks about the technological advances required for a safe transition from laboratory to clinic

Agriculture-Industry Interlinkages: Some Theoretical and Methodological Issues in the Indian Context

The inter-relationship between agriculture and industry has been a long debated issue in most of the developing countries. In the Indian context, the issue has acquired interest since the industrial stagnation of the mid 1960s. Over the years the Indian economy has undergone a structural change in its sectoral composition: from a primary agro-based economy during 1970s, the economy has emerged as predominant in the service sector since the 1990s. This structural change and uneven pattern of growth of agriculture, industry and services sector in the post reforms period is likely to appear substantial changes in the production and demand linkages among various sectors, and in turn, could have significant implication for the growth and development process of the economy. This has triggered a renewed interest in studying the inter-relationship between agriculture and industry. The present paper tries to address some of the theoretical and methodological issues in analyzing the agriculture-industry interlinkages in the Indian context

Stabilities of Quinarene Hydrocarbons

154-156The stabilities of quinarene hydrocarbons (1-9) have been studied in the light of their homodesmotic and isodesmic energies. The data point to extreme instability of these compounds

Maintaining optimal state probabilities in biological systems

A biological problem is usually studied experimentally by reducing it into a number of modules. In contrast, the systems biology approach seeks to address the collective behavior of interacting molecules vis-a-vis the corresponding higher level behavior. Various attributes of a biological system are conditionally dependent on each other, and these conditionalities are usually represented through Bayesian networks for computing easily the joint probability for a state of an attribute. In this article, a genetic algorithm is investigated to a biological system, by representing it through a Bayesian network, for evaluating the optimum state probabilities of different attributes, in order to obtain a desired joint probability for a given state of an attribute. We believe that such a study would be helpful in achieving a desired health condition by maintaining various attributes of a system to their estimated optimum levels

Proneural Basic Helix-Loop-Helix Proteins and Epidermal Growth Factor Receptor Signaling Coordinately Regulate Cell Type Specification and cdk Inhibitor Expression during Development▿

Cell differentiation and cell cycle exit are coordinately regulated during development; however, the molecular logic underlying this regulation is not known. The Drosophila cdk inhibitor Dacapo (Dap) is one of the key cell cycle regulators that exhibit dynamic expression during development and contribute to the developmental regulation of the cell cycle. In this study, regulation of Dap expression during cell type specification was investigated. The expression of Dap in the R2 and R5 precursors of the developing eye and in the newly recruited leg disc femoral sense organ precursors was found to be controlled by the epidermal growth factor receptor signaling-regulated transcription factor Pointed (Pnt) and the proneural basic helix-loop-helix proteins Atonal (Ato) and Daughterless (Da). We show that Pnt, Ato, and Da regulate Dap expression directly through their respective binding sites precisely at the time when these transcription factors function to specify neural fates. These results show that Dap expression is directly regulated by developmental mechanisms that simultaneously control cell type specification. This is potentially a general mechanism by which the expression of key cell cycle regulators is coordinated with differentiation during normal development. The direct regulation of key cell cycle regulators by the differentiation factors ensures coordinated regulation of cell cycle and differentiation

1,25-Dihydroxyvitamin D3 suppresses high glucose-induced angiotensinogen expression in kidney cells by blocking the NF-κB pathway

The renin-angiotensin system (RAS) is a major mediator of renal injury in diabetic nephropathy. Our previous studies demonstrated that 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] plays a renoprotective role by suppressing the RAS, with renin and angiotensinogen (AGT) as the main targets. The mechanism whereby 1,25(OH)2D3 transcriptionally suppresses renin gene expression has been elucidated; however, how vitamin D regulates AGT remains unknown. Exposure of mesangial cells or podocytes to high glucose (HG; 30 mM) markedly stimulated AGT expression. In mesangial cells, the stimulation was inhibited by 1,25(OH)2D3 (20 nM) or NF-κB inhibitor BAY 11–7082, suggesting the involvement of NF- κB in HG-induced AGT expression and the interaction between 1,25(OH)2D3 and NF-κB in the regulation. Plasmid pNF-κB-Luc luciferase reporter assays showed that 1,25(OH)2D3 blocked HG-induced NF-κB activity. EMSA and ChIP assays demonstrated increased p65/p50 binding to a NF-κB binding site at −1734 in the AGT gene promoter upon high glucose stimulation, and the binding was disrupted by 1,25(OH)2D3 treatment. Overexpression of p65/p50 overcame 1,25(OH)2D3 suppression, and mutation of this NF-κB binding site blunted 1,25(OH)2D3 suppression of the promoter activity. In mice lacking the vitamin D receptor, AGT mRNA expression in the kidney was markedly increased compared with wild-type mice, and AGT induction in diabetic mice was suppressed by treatment with a vitamin D analog. These data indicate that 1,25(OH)2D3 suppresses hyperglycemia-induced AGT expression by blocking NF-κB-mediated pathway