Temporal protein expression pattern in intracellular signalling cascade during T-cell activation: A computational study.

Various T-cell co-receptor molecules and calcium channel CRAC play a pivotal role in the maintenance of cell’s functional responses by regulating the production of effector molecules (mostly cytokines) that aids in immune clearance and also maintaining the cell in a functionally active state. Any defect in these co-receptor signalling pathways may lead to an altered expression pattern of the effector molecules. To study the propagation of such defects with time and their effect on the intracellular protein expression patterns, a comprehensive and largest pathway map of T-cell activation network is reconstructed manually. The entire pathway reactions are then translated using logical equations and simulated using the published time series microarray expression data as inputs. After validating the model, the effect of in silico knock down of co-receptor molecules on the expression patterns of their downstream proteins is studied and simultaneously the changes in the phenotypic behaviours of the T-cell population are predicted, which shows significant variations among the proteins expression and the signalling routes through which the response is propagated in the cytoplasm. This integrative computational approach serves as a valuable technique to study the changes in protein expression patterns and helps to predict variations in the cellular behaviour.

The emerging roles of inositol pyrophosphates in eukaryotic cell physiology.

Inositol pyrophosphates are water soluble derivatives of inositol that contain pyrophosphate or diphosphate moieties in addition to monophosphates. The best characterised inositol pyrophosphates, are IP7 (diphosphoinositol pentakisphosphate or PP-IP5), and IP8 (bisdiphosphoinositol tetrakisphosphate or (PP)2-IP4). These energy-rich small molecules are present in all eukaryotic cells, from yeast to mammals, and are involved in a wide range of cellular functions including apoptosis, vesicle trafficking, DNA repair, osmoregulation, phosphate homeostasis, insulin sensitivity, immune signalling, cell cycle regulation, and ribosome synthesis. Identified more than 20 years ago, there is still only a rudimentary understanding of the mechanisms by which inositol pyrophosphates participate in these myriad pathways governing cell physiology and homeostasis. The unique stereochemical and bioenergetic properties these molecules possess as a consequence of the presence of one or two pyrophosphate moieties in the vicinity of densely packed monophosphates are likely to form the molecular basis for their participation in multiple signalling and metabolic pathways. The aim of this review is to provide first time researchers in this area with an introduction to inositol pyrophosphates and a comprehensive overview on their cellular functions.

Esenciales en biología, patobiología y bioclínica del óxido nítrico: [revisión] / Escentials in biology, pathobiology and bioclinics of nitric oxide: [review]

El óxido nítrico es un regulador multifuncional, fundamental para diversos procesos incluyendo la inflamación, vasoregulación, señalización intra e intercelular, apoptosis y carcinogénesis. La falla en la síntesis y/o la pérdida de la biodisponibilidad de óxido nítrico es la principal característica de muchas enfermedades. La comprensión de los mecanismos subyacentes a los efectos del óxido nítrico a nivel celular y tisular, permitirá el desarrollo de nuevas terapias para balancear los efectos del óxido nítrico in vivo. El objetivo de esta revisión es mencionar los principales hallazgos en el campo de investigación relativo a este gas diatómico y su dinámica biológica...

Nitric oxide is a multifunctional regulator, which is central to diverse processes including infl ammation, vasoregulation, intra and intercellular signaling, apoptosis, and carcinogenesis. The failure in the synthesis and/or loss of bioavailability of nitric oxide is the main characteristic of many diseases. Understanding the mechanisms underlying the effects of nitric oxide at the cellular and tissue level, will allow the development of new therapies to balance the effects of nitric oxide in vivo. The purpose of this review is to mention the key findings in the field of research on this diatomic gas and their biological dynamics...

Mitogenic response of rat lung and tracheal epithelial cells in monolayer primary cultures—Modulation of TNF-α expression.

Epithelial cells isolated from rat lung and trachea were grown on monolayers and their response to a number of hormones and growth factors were studied. Maximum proliferative response in serum containing media was observed when insulin, cholera toxin and cortisol were present together. However, these additives when present independently showed a marginal response. The synergism, due to these factors in promoting growth was seen very early in culture (day 4) as shown by thymidine labelling studies, On examining the indices of early mitogenesis, such as the expression of c-myc, our data suggests that these factors stimulate the expression of c-myc within 4 h. With respect to expression of TNF-α mRNA, this study suggests a possible modulation of TNF-α expression in response to these mitogens that stimulate proliferation maximally. Whether this expression of TNF-α by these epithelial cells is due to a maximal proliferative stimulus and/or is an early step in the cascade of intracellular signalling events is to be investigated in detail.

The fate of a cell is the function of its position and vice-versa.

Developmental biologists distinguish between mosaic embryos, in which the removal of a cell or group of cells results in a defective adult, and regulative embryos, in which the adult appears normal in spite of such removal. I suggest that the mosaic/regulative distinction is best viewed by contrasting within-cell signals (i.e., a cell can develop autonomously, perhaps on the basis of instructions derived from the mother) against between-cell signals (i.e., development, and the origin of form and shape, is based on intercellular communication). This distinction is not rigid; the same embryo can make use of both within-cell and between-cell signals. During evolution, signalling between cells is likely to have become advantageous as organisms increased in size. However, the fact that an embryo displays regulative behaviour may be an automatic consequence of the way it develops rather than an evolved adaptation.