Cycling Temporal response

Cycling protein phosphorylation plays a role in the mammalian circadian clock as well. PERI, PER2 and BMAL all show temporal changes in electrophoretic mobility that are eliminated by phosphatase treatment (Lee et al 2001). Although these PER phosphorylations are likely to reflect CKl activity they may not be the only clock-related substrates of this enzyme family. CRYl and CRY2, for instance, can be phosphorylated by CKls in vitro when present in a CRY/PER/CKle complex (Eide et al 2002). Two isoforms of mammalian CLOCK (orthologue of Drosophila CLK) also appear to be phosphorylated, resulting in mobility shifts by Western analysis (Lee et al 2001). The kinase(s) responsible for CLOCK phosphorylation is (are) unknown. 

A recent paper clearly highlighted the limitations of in vitro systems in modeling whole-organism responses, which should be considered when developing biomarkers of in vivo toxicity. Dere and colleagues (58) compared the temporal gene expression profiles of Hepalclc mouse hepatoma cells and of the mice liver after treatment with a dioxin. The analysis revealed that Hepalclc cells were able to model the induction of xenobiotic metabolism in vivo. On the other hand, responses associated with cell cycle progression and proliferation were unique to the in vitro system, while lipid metabolism and immune responses were not replicated effectively in the Hepalclc cells. 

Fig. 4. The temporal sequence of events when a resting strip of tracheal smooth muscle is activated by carbacholamine addition at 10 min. There is a transient rise in [Ca2+]c (—) followed by a transient increase in the content (—) of phosphorylated myosin light chains (MLC-P) which lead in turn to the initiation of force development (—). Increased force is sustained even though the content of MLC-P declines. Preceding the sustained phase of force maintenance, there is an increase in the phosphorylation of desmin (D-P), synemin (S-P), caldesmon (CD-P) and a number of low molecular weight cytosolic proteins (X-P). These remain phosphorylated throughout the sustained phase of the response during which there is a sustained increase in Ca2+ cycling across the plasma membrane which regulates the activity of the membrane-associated protein kinase C.

There is much evidence for arsenic release into shallow sediment pore waters and overlying surface waters in response to temporal variations in redox conditions. Sullivan and Aller (1996) investigated arsenic cycling in shallow sediments from an unpolluted area of the Amazonian offshore shelf. They found pore-water arsenic concentrations up to 300 p.g in anaerobic sediments with nearly coincident peaks of dissolved arsenic and iron. The peaks for iron concentration were often slightly above those of arsenic (Figure 1). The magnitude of the peaks and their depths varied from place to place and possibly seasonally but were typically between 50 cm and 150 cm beneath the sediment-water interface (Sullivan and Aller, 1996). There was no correlation between pore-water arsenic concentrations and sediment arsenic concentrations (Figure 1). 

Biomarkers are often used in test batteries to evaluate the effects of exposure to multiple sources of contaminants and to detect responses to various sources of pollution, such as harbours, miscellaneous industrial sites and municipal and hospital wastewaters. Field studies with biomarkers are often plagued by various constraints, such as spatial variation (e.g. change in habitat characteristics), temporal variation (e.g. cycle of reproduction) and availability of organisms that can hamper data acquisition and prevent the use of multivariate methods during... 

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