Tribbles: novel regulators of cell function; evolutionary aspects

Identification of rate-limiting steps or components of intracellular second messenger systems holds promise to effectively interfere with these pathways under pathological conditions. The emerging literature on a recently identified family of signalling regulator proteins, called tribbles gives interesting clues for how these proteins seem to link several ‘independent’ signal processing systems together. Via their unique way of action, tribbles co-ordinate the activation and suppression of the various interacting signalling pathways and therefore appear to be key in determining cell fate while responding to environmental challenges. This review summarises our current understanding of tribbles function and also provides an evolutionary perspective on the various tribbles genes. Received 10 January 2006; received after revision 20 March 2006; accepted 5 April 2006     

Optimization of the cellular import of functionally active SH2-domain-interacting phosphopeptides

Phosphopeptides interacting with src homology 2 (SH2) domains can activate essential signaling enzymes in vitro. When delivered to cells, they may disrupt protein-protein interactions, thereby influencing intracellular signaling. We showed earlier that phosphopeptides corresponding to the inhibitory motif of Fcγ receptor IIb and a motif of the Grb2-associated binder 1 adaptor protein activate SH2-containing tyrosine phosphatase 2 in vitro. To study the ex vivo effects of these peptides, we have now compared different methods for peptide delivery: (i) permeabilization of the target cells and (ii) the use of cell-permeable vectors, which are potentially able to transport biologically active compounds into B cells. We found octanoyl-Arg₈ to be an optimal carrier for the delivery of phosphopeptides to the cells. With this strategy, the function of cell-permeable SHP-2-binding phosphopeptides was analyzed. These peptides modulated the protein phosphorylation in B cells in a dose- and time-dependent manner. Received 27 July 2006; received after revision 4 September 2006; accepted 18 September 2006     

Sperm viability in the reproductive tract of females in a population of Sceloporus mucronatus exhibiting asynchronous reproduction

Asynchronous reproduction is a common phenomenon in high-elevation populations of lizards from Central México. Sperm storage in the reproductive tract of females is the mechanism for making oocyte fertilization possible. Our study addresses questions related to functional oviductal sperm storage of females mating on different dates throughout the reproductive season. A population of Sceloporus mucronatus with copulation in the summer and ovulation in the fall was chosen for this experiment. Eleven females that copulated in the field during June and 13 females that copulated in captivity during August were maintained in the laboratory until parturition. The number of pregnant females and the litter sizes produced in each experimental group were indicative of the viability of the stored sperm. Sperm stored in the reproductive tract of females were able to fertilize eggs after 4 months. No significant differences were found in the number of pregnant females between the 2 experimental groups nor in the litter sizes that they produced. We found that the amount of time sperm were held in the female reproductive tract (ca. 3 months) had no effect on the capacity of sperm to fertilize eggs. Histological examination of 8 oviducts collected before the mating season eliminated the possibility of sperm storage from one year to the next. In this system, sperm retention could have evolved as a response mechanism to deal with the asynchrony between sexes in the reproductive cycles. However, we cannot rule out alternative hypotheses.     

Small G proteins are expressed ubiquitously in lymphoid cells and do not correspond to Bcl-2

The bcl-2 gene is consistently associated with t(14; 18) chromosomal translocations observed in a large fraction of human B-cell lymphomas. The t(14; 18) translocation results in deregulated expression of the bcl-2 gene and synthesis of inappropriately high levels of the Bcl-2 protein. Gene transfer studies suggest a role for Bcl-2 in cell survival, growth enhancement and oncogenic transformation. To test the suggestion that GTP-binding by Bcl-2 may mediate its biological effects we characterized the GTP-binding proteins in lymphoid cells expressing Bcl-2. Expression of several small GTP-binding proteins was found to be ubiquitous and did not vary with levels of Bcl-2. By using immunological, electrophoretic and cell-fractionation techniques, we separated Bcl-2 from G proteins of small relative molecular mass (Mr) and showed that it is incapable of binding GTP. Our results show that small Mr G proteins are widely expressed in lymphoid cells and that Bcl-2 is not a novel member of this GTP-binding protein family.     

二自由度自谐式机器人动力学的研究

本文对引用弹性元件的二自由度谐式机器人的动力学进行了分析,在该模型中引入了负反馈系统。按预期的机构运动规律和系统的稳定性要求,研究了反馈放大系数的合理选择,并对构件单独和同时运动的仿真图线进行了分析。