To charge or not to charge?

The ability to engineer proteins with increased thermostability will profoundly broaden their practical applications. Recent experimental results show that optimization of charge-charge interactions on the surface of proteins can be a useful strategy in the design of thermostable enzymes. Results also indicate a possibility that such optimized interactions provide structural determinants for enhanced stability of proteins from thermophilic organisms. In this article, the general strategy for design of thermostable proteins and perspectives for future studies are discussed.     

To model or not to model?

In theory, the combination of mathematical modeling with experimental studies can be a powerful and compelling approach to understanding cell biology. In practice, choosing appropriate problems, identifying willing and able collaborators, and publishing the resulting research can be remarkably challenging. To provide perspective on the question of whether and when to combine modeling and experiments, a panel of experts at the 2010 ASCB Annual Meeting shared their personal experiences and advice on how to use modeling effectively.     

The somatopause: to treat or not to treat?

There is much evidence that some aspects of ageing are similar to those observed in selective hormone deficiencies during adulthood. Replacement therapy in hypogonadism and/or growth hormone (GH) deficiency in adulthood is very successful in reversing the related clinical symptomatology. However, preliminary studies of GH treatment in the normal elderly have been largely disappointing: an increase in muscle mass is only accompanied by improved muscle strength if exercise is also increased during this period. No real benefit of GH therapy, additional to that of exercise, has been reported. Epidemiological studies indicate a relationship between high-normal insulin-like growth factor-I levels and cancer development. No definitive answers can presently be given regarding the safety of long-term GH therapy in otherwise healthy individuals during the somatopause.     

Atrial fibrillation: to map or not to map?

Isolation of the pulmonary veins may be an effective treatment modality for eliminating atrial fibrillation (AF) episodes but unfortunately not for all patients. When ablative therapy fails, it is assumed that AF has progressed from a trigger-driven to a substrate-mediated arrhythmia. The effect of radiofrequency ablation on persistent AF can be attributed to various mechanisms, including elimination of the trigger, modification of the arrhythmogenic substrate, interruption of crucial pathways of conduction, atrial debulking, or atrial denervation. This review discusses the possible effects of pulmonary vein isolation on the fibrillatory process and the necessity of cardiac mapping in order to comprehend the mechanisms of AF in the individual patient and to select the optimal treatment modality.     

To be or not to be ubiquitinated?

Levels of p21, a cyclin-dependent kinase (CDK) inhibitor, are controlled in part at the post-translational level by protein degradation. Although the signaling pathways leading to p21 degradation have not yet been fully elucidated, it is evident that p21 ubiquitination is an essential factor in its degradation. We discuss that, with the only notable exception of ornithine decarboxylase, ubiquitination appears to be a prerequisite for proteasomal degradation rather than an unnecessary byproduct of such proteolysis.     

Myosins in melanocytes: to move or not to move?

The actin network has been implicated in the intracellular transport and positioning of the melanosomes, organelles that are specialized in the biosynthesis and the storage of melanin. It contributes also to molecular mechanisms that underlie the intracellular membrane dynamics and thereby can control the biogenesis of melanosomes. Two mechanisms for actin‐based movements have been identified: one is dependent on the motors associated to actin namely the myosins; the other is dependent on actin polymerization. This review will focus on to the role of the actin cytoskeleton and myosins in the transport and in the biogenesis of melanosomes. Myosins involved in membrane traffic are largely seen as transporters of organelles or membrane vesicles containing cargos along the actin networks. Yet increasing evidence suggests that some of the myosins contribute to the dynamics of internal membrane by using other mechanisms. The role of the myosins and the different molecular mechanisms by which they contribute or may contribute to the distribution, the movement and the biogenesis of the melanosomes in epidermal melanocytes and retinal pigmented epithelial (RPE) cells will be discussed.     

Adaptation to stress in yeast: to translate or not?

For most eukaryotic organisms, including Saccharomyces cerevisiae, the rapid inhibition of protein synthesis forms part of a response to stress. In order to balance the changing conditions, precise stress-specific alterations to the cell's proteome are required. Therefore, in the background of a global down-regulation in protein synthesis, specific proteins are induced. Given the level of plasticity required to enable stress-specific alterations of this kind, it is surprising that the mechanisms of translational regulation are not more diverse. In the present review, we summarize the impact of stress on translation initiation, highlighting both the similarities and distinctions between various stress responses. Finally, we speculate as to how yeast cells generate stress-responsive programmes of protein production when regulation is focused on the same steps in the translation pathway.