Exocytotic fusion is activated by Rab3a peptides.

Studies of intracellular traffic in yeast and mammalian systems have implicated members of the Rab family of small GTP-binding proteins as regulators of membrane fusion. We have used the patch clamp technique to measure exocytotic fusion events directly and investigate the role of GTP-binding proteins in regulating exocytosis in mast cells. Intracellular perfusion of mast cells with GTP-gamma S is sufficient to trigger complete exocytotic degranulation in the absence of other intracellular messengers. Here we show that GTP is a potent inhibitor of GTP-gamma S-induced degranulation, indicating that sustained activation of a GTP-binding protein is sufficient for membrane fusion. We have found that synthetic oligopeptides, corresponding to part of the effector domain of Rab3a, stimulate complete exocytotic degranulation, similar to that induced by GTP-gamma S. The response is selective for Rab3a sequence and is strictly dependent on Mg2+ and ATP. This suggests that sustained activation of a Rab3 protein causes exocytotic fusion. The peptide response can be accelerated by GDP-beta S, suggesting that Rab3a peptides compete with endogenous Rab3 proteins for a binding site on a target effector protein, which causes fusion on activation.     

Traditional versus novel forecasting techniques: how much do we gain?

This article applies two novel techniques to forecast the value of US manufacturing shipments over the period 1956–2000: wavelets and support vector machines (SVM). Wavelets have become increasingly popular in the fields of economics and finance in recent years, whereas SVM has emerged as a more user‐friendly alternative to artificial neural networks. These two methodologies are compared with two well‐known time series techniques: multiplicative seasonal autoregressive integrated moving average (ARIMA) and unobserved components (UC). Based on forecasting accuracy and encompassing tests, and forecasting combination, we conclude that UC and ARIMA generally outperform wavelets and SVM. However, in some cases the latter provide valuable forecasting information that it is not contained in the former. Copyright © 2008 John Wiley & Sons, Ltd.     

Anti-infective properties of bacteriocins: an update

Bacteriocin production is a widespread phenomenon among bacteria. Bacteriocins hold great promise for the treatment of diseases caused by pathogenic bacteria and could be used in the future as alternatives to existing antibiotics. The anti-infective potential of bacteriocins for inhibiting pathogens has been shown in various food matrices including cheese, meat, and vegetables. However, their inhibition of pathogens in vivo remains unclear and needs more investigation, due mainly to difficulties associated with demonstrating their health benefits. Many bacteriocins produced by established or potential probiotic organisms have been evaluated as potential therapeutic agents and interesting findings have been documented in vitro as well as in a few in vivo studies. Some recent in vivo studies point to the efficacy of bacteriocin-based treatments of human and animal infections. While further investigation remains necessary before the possibilities for bacteriocins in clinical practice can be described more fully, this review provides an overview of their potential applications to human and veterinary health.     

Tumor necrosis factor α in the pathogenesis of cerebral malaria

Physiologically in the brain, cytokines such as tumor necrosis factor-alpha (TN) are released by the immune system and can modulate neurological responses. Conversely, the central nervous system (CNS) is also able to modulate cytokine production. In the case of CNS disorders, cytokine release may be modified. Cerebral malaria (CM) is a complication of Plasmodium falciparum infection in humans and is characterized by a reversible encephalopathy with seizures and loss of consciousness. Central clinical signs are partly due to sequestration of parasitized red blood cells in the brain microvasculature due to interactions between parasite proteins and adhesion molecules. TNF is produced and released by host cells following exposure to various malarial antigens. The increase of TNF release is responsible for the overexpression of adhesion molecules. This article reviews the involvement of TNF in cerebral malaria and the relation with all the processes involved in this pathology. It shows that (i) TNF levels are increased in plasma and brain but with no clear correlation between TNF levels and occurrence and severity of CM; (ii) TNF is responsible for intercellular adhesion molecule-1 upregulation in CM, the relation being less clear for other adhesion molecules; (iii) TNF receptors are upregulated in CM, with TNF receptor 2 (TNFR2) showing a higher upregulation than TNFR1 in vivo; (iv) in murine CM, low doses of TNF seem to protect from CM, whereas excess TNF induces CM and anti-TNF therapies (antibodies, pentoxifylline) did not show any efficiency in protection from CM. Moreover, the involvement of lymphotoxin a, which shares with TNF the same receptors with similar affinity, appears to be an interesting target for further investigation.Received 4 December 2002; received after revision 7 February 2003; accepted 14 February 2003     

Separation of cardiotonic from flavanoid compounds of the squill,Urginea maritima baker

Resumen Se describe un método de filtración sencilla a través de poliamidas, con el cual se han conseguido los mejores resultados en la separación de los glucósidos cardiotónicos y flavonoides de las preparaciones de escila.