Wayne Rasband of NIH has created ImageJ, an open source Java-written program that is now at version 1.31 and is used for many imaging applications, including those that that span the gamut from skin analysis to neuroscience. ImageJ is in the public domain and runs on any operating system (OS). ImageJ is easy to use and can do many imaging manipulations. A very large and knowledgeable group makes up the user community for ImageJ. Topics covered are imaging abilities; cross platform; image formats support as of June 2004; extensions, including macros and plug-ins; and imaging library. NIH reports tens of thousands of downloads at a rate of about 24,000 per month currently. ImageJ can read most of the widely used and significant formats used in biomedical images. Manipulations supported are read/write of image files and operations on separate pixels, image regions, entire images, and volumes (stacks in ImageJ). Basic operations supported include convolution, edge detection, Fourier transform, histogram and particle analyses, editing and color manipulation, and more advanced operations, as well as visualization. For assistance in using ImageJ, users e-mail each other, and the user base is highly knowledgeable and will answer requests on the mailing list. A thorough manual with many examples and illustrations has been written by Tony Collins of the Wright Cell Imaging Facility at Toronto Western Research Institute and is available, along with other listed resources, via the Web.

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Image processing with ImageJ

Capsaicin, the main pungent ingredient in 'hot' chilli peppers, elicits a sensation of burning pain by selectively activating sensory neurons that convey information about noxious stimuli to the central nervous system We have used an expression cloning strategy based on calcium influx to isolate a functional cDNA encoding a capsaicin receptor from sensory neurons This receptor is a non-selective cation channel that is structurally related to members of the TRP family of ion channels The cloned capsaicin receptor is also activated by increases in temperature in the noxious range, suggesting that it functions as a transducer of painful thermal stimuli in vivo

/pdf/the-capsaicin-receptor-a-heat-activated-ion-channel-in-the-57mhjl9hkd.pdf

The capsaicin receptor: a heat-activated ion channel in the pain pathway

Protein kinase C has a crucial role in signal transduction for a variety of biologically active substances which activate cellular functions and proliferation. When cells are stimulated, protein kinase C is transiently activated by diacylglycerol which is produced in the membrane during the signal-induced turnover of inositol phospholipids. Tumour-promoting phorbol esters, when intercalated into the cell membrane, may substitute for diacylglycerol and permanently activate protein kinase C. The enzyme probably serves as a receptor for the tumour promoters. Further exploration of the roles of this enzyme may provide clues for understanding the mechanism of cell growth and differentiation.

The role of protein kinase C in cell surface signal transduction and tumour promotion

Inositol trisphosphate is a second messenger that controls many cellular processes by generating internal calcium signals. It operates through receptors whose molecular and physiological properties closely resemble the calcium-mobilizing ryanodine receptors of muscle. This family of intracellular calcium channels displays the regenerative process of calcium-induced calcium release responsible for the complex spatiotemporal patterns of calcium waves and oscillations. Such a dynamic signalling pathway controls many cellular processes, including fertilization, cell growth, transformation, secretion, smooth muscle contraction, sensory perception and neuronal signalling.

Inositol trisphosphate and calcium signalling

There has recently been rapid progress in understanding receptors that generate intracellular signals from inositol lipids. One of these lipids, phosphatidylinositol 4,5-bisphosphate, is hydrolysed to diacylglycerol and inositol trisphosphate as part of a signal transduction mechanism for controlling a variety of cellular processes including secretion, metabolism, phototransduction and cell proliferation. Diacylglycerol operates within the plane of the membrane to activate protein kinase C, whereas inositol trisphosphate is released into the cytoplasm to function as a second messenger for mobilizing intracellular calcium.

Inositol trisphosphate, a novel second messenger in cellular signal transduction.

http://www.biochemsoctrans.org/content/17/1/94.full.pdf

Effects of the Ca2+-mobilizing tumour promotor thapsigargin and an inositol trisphosphate mobilizing agonist on cytosolic Ca2+ in bovine adrenal chromaffin cells

A large number of diseases are caused by defects in signalling pathways. The nature of these defects and how they are induced varies enormously. Pathogenic organisms and viruses, many of which can interfere with signalling events, can cause some of these defects. There are other diseases that can be traced to defects in the function of cell signalling pathways. The concept of signalsome remodelling and disease provides a framework for considering how defects in signalling pathways can result in disease. It is convenient to separate these defects into phenotypic remodelling of the signalsome and genotypic remodelling of the signalsome. Most of the serious diseases in humans, such as hypertension, heart disease, diabetes and many forms of mental illness, seem to arise from subtle phenotypic modifications of signalling pathways. Such phenotypic remodelling alters the behaviour of cells so that their normal functions are subverted, leading to disease. Since it has proved difficult to clearly establish this relationship between signalsome remodelling and disease, there has been relatively little progress in designing effective treatments. Genotypic modifications resulting from either somatic mutations or germline mutations have been somewhat easier to diagnose, but have also proved difficult to treat as witnessed by the failure of many of the gene therapy strategies. Clearly, there is an urgent need to understand more about all of these disease states in order to design better therapies. The enormous redundancy built into cell signalling mechanisms offers many opportunities for discovering new ways of correcting many disease states. The reversal of Ca2+-dependent neurodegeneration is an example where such a strategy could provide novel therapies for treating some of the major neural diseases in humans such as Alzheimer9s disease and Parkinson9s disease.

http://www.biochemj.org/csb/csb/012/012.pdf

Signalling Defects and Disease

1. Fluid secretion by isolated salivary glands was stimulated by elevating the external potassium concentration. 2. The stimulatory effect of potassium was dependent on external calcium and was potentiated by a subthreshold dose of 5-hydroxytryptamine (5-HT). 3. During the action of 120 mM potassium there was a large calciumdependent decrease in transepithelial resistance similar to that produced with 5-HT at normal potassium concentrations. 4. These results on Calliphora salivary glands are compared with other cases where cells are activated by high potassium. In most cases, the effect of high potassium is dependent upon calcium, suggesting that the latter plays a primary role in cell activation.

Stimulus-secretion coupling in an insect salivary gland: cell activation by elevated potassium concentrations.

Erratum: Regulation of fertilization-induced Ca2+spiking in the mouse zygote ()

Inositol lipids play a central role in the signal transduction mechanism used by a large number of hormones and neurotransmitters. The primary action of these agonists is to stimulate the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) to produce diacylglycerol (DG), which remains in the plane of the membrane, and inositol 1,4,5-trisphosphate (IP3), which is released to the cytoplasm (for details see Michell, Chapter 6). The fascinating aspect of this receptor mechanism is that both products resulting from the agonist-dependent cleavage of PIP2 appear to function as second messengers to activate separate cellular processes. The neutral DG activates a protein kinase (C-kinase) that phosphorylates specific proteins (Takai et al., 1979; Kishimoto et al., 1980; Kuo et al., 1980; Nishizuka, 1983), whereas IP3 appears to function as a second messenger to mobilize intracellular calcium (Berridge, 1983; Streb et al., 1983; Berridge et al., 1984b; Burgess et al., 1984; Joseph et al., 1984).

Michael J. Berridge

Papers

Effects of the Ca2+-mobilizing tumour promotor thapsigargin and an inositol trisphosphate mobilizing agonist on cytosolic Ca2+ in bovine adrenal chromaffin cells

Signalling Defects and Disease

Stimulus-secretion coupling in an insect salivary gland: cell activation by elevated potassium concentrations.

Erratum: Regulation of fertilization-induced Ca2+spiking in the mouse zygote ()

Inositol Trisphosphate and Diacylglycerol as Intracellular Second Messengers