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

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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.

The universality of calcium as an intracellular messenger depends on its enormous versatility. Cells have a calcium signalling toolkit with many components that can be mixed and matched to create a wide range of spatial and temporal signals. This versatility is exploited to control processes as diverse as fertilization, proliferation, development, learning and memory, contraction and secretion, and must be accomplished within the context of calcium being highly toxic. Exceeding its normal spatial and temporal boundaries can result in cell death through both necrosis and apoptosis.

The versatility and universality of calcium signalling

Ca2+ is a highly versatile intracellular signal that operates over a wide temporal range to regulate many different cellular processes. An extensive Ca2+-signalling toolkit is used to assemble signalling systems with very different spatial and temporal dynamics. Rapid highly localized Ca2+ spikes regulate fast responses, whereas slower responses are controlled by repetitive global Ca2+ transients or intracellular Ca2+ waves. Ca2+ has a direct role in controlling the expression patterns of its signalling systems that are constantly being remodelled in both health and disease.

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Calcium signalling: dynamics, homeostasis and remodelling

Inositol 1,4,5-trisphosphate is a second messenger which regulates intracellular calcium both by mobilizing calcium from internal stores and, perhaps indirectly, by stimulating calcium entry. In these actions it may function with its phosphorylated metabolite, inositol 1,3,4,5-tetrakisphosphate. The subtlety of calcium regulation by inositol phosphates is emphasized by recent studies that have revealed oscillations in calcium concentration which are perhaps part of a frequency-encoded second-messenger system.

Michael J. Berridge

Papers

Inositol trisphosphate and calcium signalling

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

The versatility and universality of calcium signalling

Calcium signalling: dynamics, homeostasis and remodelling

Inositol phosphates and cell signalling