Biomedical subjects

Jane E Swatton

Publications and source records attributed to Jane E Swatton.

3 recordsLinked to original sources

PubMed2005

Cell-cell communication in Gram-negative bacteria.

Over the last decade or so, a wealth of research has established that bacteria communicate with one another using small molecules. These signals enable the individuals in a population to coordinate their behaviour. In the case of pathogens, this behaviour may include decisions such as when to attack a host organism or form a biofilm. Consequently, such signalling systems are excellent targets for the development of new antibacterial therapies. In this review, we assess how Gram-negative bacteria use small molecules for cell-cell communication, and discuss the main approaches that have been developed to interfere with it.

Cell Communication↗

PubMed2004

Increased MAP kinase activity in Alzheimer's and Down syndrome but not in schizophrenia human brain.

Abnormal phosphorylation of tau is a feature of Alzheimer's disease (AD), which develops prematurely in Down syndrome (DS) patients. Cognitive impairment is also recognized as a clinical characteristic of schizophrenia, which does not appear to be associated with tau-aggregate formation. Several kinases can phosphorylate tau in cell-free assays. Here we show increased activity of mitogen-activated protein kinases (MAPKs) (including ERK1/2, SAPKs and p38) in post mortem AD and DS brains, which could not be accounted for by expression changes. In contrast, glycogen synthase kinase-3 activity (GSK-3 alpha beta) was reduced significantly. Examination of tau in AD and DS using antibodies selective for MAPK phosphorylation sites showed increased immunoreactivity. In addition, phosphorylation of S(199), reportedly a selective substrate for cyclin-dependent kinase-5 (cdk5) or GSK-3 alpha beta was only observed in AD samples, which showed a concomitant increase in the expression of p25, the enhancing cofactor for cdk5 activity. However, in schizophrenia brain, MAPK-phosphorylated tau was unchanged compared to matched controls, despite similar expression levels to those in AD. The activities of the MAPKs and GSK-3 alpha beta were also unchanged. These data demonstrate that in AD and DS, enhanced MAPK activity, which has an established role in regulating neuronal plasticity and survival, can account for irregular tau phosphorylation, and that the molecular processes involved in these neurodegenerative disorders are distinct from those in schizophrenia. These data also question the significance of GSK-3 alpha beta, as much previous work carried out in vitro has placed this kinase as a favoured candidate for involvement in the pathological phosphorylation of tau.

Aged↗

PubMed2002

Fast biphasic regulation of type 3 inositol trisphosphate receptors by cytosolic calcium.

In cytosol-like medium (CLM) with a free [Ca(2+)] of 200 nm, a supramaximal concentration of inositol 1,4,5-trisphosphate (IP(3)) (30 microm) evoked (45)Ca(2+) release from type 3 IP(3) receptors only after a latency of 48 +/- 6 ms; this latency could not be reduced by increasing the IP(3) concentration. In CLM containing a low free [Ca(2+)] ( approximately 4 nm), 300 microm IP(3) evoked (45)Ca(2+) release after a latency of 66 +/- 11 ms; this was reduced to 14 +/- 3 ms when the [Ca(2+)] was 1 mm. Preincubation with CLM containing 100 microm Ca(2+) caused a rapid (half-time = 33 +/- 9 ms), complete, and fully reversible inhibition that could not be overcome by a high concentration of IP(3) (300 microm). Hepatic (type 2) IP(3) receptors were not inhibited by Ca(2+) once they had bound IP(3), but 100 microm Ca(2+) rapidly inhibited type 3 IP(3) receptors whether it was delivered before addition of IP(3) or at any stage during a response to IP(3). Ca(2+) increases the affinity of IP(3) for hepatic receptors by slowing IP(3) dissociation, but Ca(2+) had no effect on IP(3) binding to type 3 receptors. The rate of inhibition of type 3 IP(3) receptors by Ca(2+) was faster than the rate of IP(3) dissociation, and occurred at similar rates whether receptors had bound a high (adenophostin) or low affinity (3-deoxy-3-fluoro-IP(3)) agonist. Dissociation of agonist is not therefore required for Ca(2+) to inhibit type 3 IP(3) receptors. We conclude that type 2 and 3 IP(3) receptors are each biphasically regulated by Ca(2+), but by different mechanisms. For both, IP(3) binding causes a stimulatory Ca(2+)-binding site to be exposed allowing Ca(2+) to bind and open the channel. IP(3) binding protects type 2 receptors from Ca(2+) inhibition, but type 3 receptors are inhibited by Ca(2+) whether or not they have IP(3) bound. Increases in cytosolic [Ca(2+)] will immediately inhibit type 3 receptors, but inhibit type 2 receptors only after IP(3) has dissociated.

Animals↗