Acute regulation of the tumour suppressor phosphatase, PTEN, by anionic lipids and reactive oxygen species.

PTEN (phosphatase and tensin homologue deleted on chromosome 10) is a member of the protein tyrosine phosphatase family that is structurally adapted to facilitate the metabolism of 3-phosphoinositide lipid second messengers, especially PtdIns(3,4,5) P (3). Cellular PTEN activity is restrained by the retention of C-terminally phosphorylated enzyme in the cytosol. Dephosphorylation by as yet undefined phosphatases initiates an electrostatic switch which targets PTEN specifically to the plasma membrane, where it binds through multiple positively charged residues in both the C2 and N-terminal domains and is susceptible to feedback regulation through proteolytic degradation. PTEN also forms signalling complexes with PDZ domain-containing adaptors, such as the MAGUK (membrane-associated guanylate kinase) proteins, interactions which appear to be necessary for metabolism of localized pools of PtdIns(3,4,5) P (3) involved in regulating actin cytoskeleton dynamics. TPIP [TPTE (transmembrane phosphatase with tensin homology) and PTEN homologous inositol lipid phosphatase] is a novel gene product which exists in multiply spliced forms. TPIPalpha has PtdIns(3,4,5) P (3) 3-phosphatase activity and is localized to the endoplasmic reticulum, via two transmembrane spanning regions, where it may metabolize PtdIns(3,4,5) P (3) that appears to be unaffected by expressed PTEN. PTEN can be acutely regulated by oxidative stress and by endogenously produced reactive oxygen species. This mechanism provides a novel means to stimulate phosphoinositide 3-kinase-dependent signalling pathways, which may be important in circumstances where PtdIns(3,4,5) P (3) and oxidants are produced concurrently.

An accurate approach to the design of channel hydraulic flocculators.

The design of flocculators for water treatment continues to be based on the generalized and simplistic concept of mean velocity gradient within the reaction zone. This approach makes little sense for hydraulic flocculators in which the turbulence conditions are heterogenous. A theoretical, experimental and computational fluid dynamics study is presented, in which a point-to-point approach is derived, allowing variations in turbulent kinetic energy to be taken into account in determining flocculation efficiency. Results for the point-to-point calculation are compared with experimental measurements of flocculation efficiency in a full-scale model of a channel hydraulic flocculator, and an extremely good fit is obtained, demonstrating the point-to-point approach to be an accurate method of determining flocculation efficiency in channel hydraulic flocculators. A design example is presented showing how the point-to-point approach can be used in practice. It is concluded that the point-to-point approach is a much better method of design than that based on the mean velocity gradient.

Antagonism of PI 3-kinase-dependent signalling pathways by the tumour suppressor protein, PTEN.

The tumour suppressor protein, PTEN (phosphatase and tensin homologue deleted on chromosome 10) is a member of the mixed function, serine/threonine/tyrosine phosphatase subfamily of protein phosphatases. Its physiological substrates, however, are primarily 3-phosphorylated inositol phospholipids, which are products of phosphoinositide 3-kinases. PTEN thus antagonizes PI 3-kinase-dependent signalling pathways, which explains to a large extent its tumour suppressor status. We have examined the kinetic behaviour, substrate specificity and regulation of PTEN both in vitro and in a variety of cellular models. Although PTEN can utilize both phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P(3)] and its water-soluble headgroup, inositol 1,3,4,5-tetrakisphosphate, as substrates, it displays classical features of interfacial catalysis, which greatly favour the lipid substrate (by as much as 1000-fold as judged by K(cat)/K(m) values). Expression of PTEN in U87 cells (which lack endogenous PTEN) and measuring the levels of all known 3-phosphorylated lipids suggests that phosphatidylinositol 3,4-bisphosphate and PtdIns(3,4,5)P(3) are both substrates, but that phosphatidylinositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate are not. PTEN binds to several PDZ-domain-containing proteins via a consensus sequence at its extreme C-terminus. Disruption of targeting to PDZ-domain proteins selectively blocks some PTEN functions, but not others, suggesting the existence of spatially localized, functionally dedicated pools of signalling lipids. We have also shown recently that PTEN expression is controlled at the transcriptional level and is profoundly upregulated by peroxisome proliferator activated receptor gamma agonists, thereby providing possible implications for these drugs in diabetes, inflammation and cancer.

The effects of child behavior problems on the maintenance of intervention fidelity.

Maintenance of behavior change has been considered a crucial, through largely unrealized, goal of behavioral interventions. One often overlooked factor is that before interventions can be successful and durable, the intervention protocol must be implemented as planned. This study investigated the effects of child behavior problems on the maintenance of intervention fidelity by teachers across two intervention protocols: escape extinction and functional communication training. A high rate of behavior problems during escape extinction appeared to punish teachers' efforts, and fidelity deteriorated. In contrast, there was a low rate of behavior problems during functional communication training. Teachers maintained high protocol fidelity and those sessions were less stressful and more productive. We propose that intervention protocols can be differentiated by the costs associated with implementing them faithfully. Protocols designed to be user friendly will be more likely to produce high fidelity, and therefore, durable intervention gains.

Adsorption of the cyanobacterial hepatotoxin microcystin-LR by a low-cost activated carbon from the seed husks of the pan-tropical tree, Moringa oleifera.

A low-cost activated carbon from the pan-tropical multipurpose tree Moringa oleifera removes the cyanobacterial hepatotoxin microcystin-LR in quantitative amounts from water in batch adsorption trials. The potential of M. oleifera seed husk carbon for cyanobacterial toxin removal in drinking water treatment in tropical countries is discussed.

Facilitated communication: a failure to replicate the phenomenon.

Twenty-one subjects participated in a study of Biklen's and Crossley's hypothesis that persons with autism show unexpected literacy and improved communication ability through the process of facilitated communication (FC). Repeated measures of literacy were conducted at (a) a baseline test of communicative ability before FC; (b) a pretest with facilitation; and (c) a posttest with facilitation after 20 hours of training. At both the pretest and posttest, the facilitators were screened from hearing or seeing the questions or pictorial stimuli. Although some facilitators reported newfound communicative abilities during training sessions, no client showed unexpected literacy or communicative abilities when tested via the facilitator screening procedure, even after 20 hours of training. Separate analyses indicated that some facilitators influenced the communicative output of their clients.