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.     

Hypoxia and Fungal Pathogenesis: To Air or Not To Air?

Over the last 3 decades, the frequency of life-threatening human fungal infections has increased as advances in medical therapies, solid-organ and hematopoietic stem cell transplantations, an increasing geriatric population, and HIV infections have resulted in significant rises in susceptible patient populations. Although significant advances have been made in understanding how fungi cause disease, the dynamic microenvironments encountered by fungi during infection and the mechanisms by which they adapt to these microenvironments are not fully understood. As inhibiting and preventing in vivo fungal growth are main goals of antifungal therapies, understanding in vivo fungal metabolism in these host microenvironments is critical for the improvement of existing therapies or the design of new approaches. In this minireview, we focus on the emerging appreciation that pathogenic fungi like Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus are exposed to oxygen-limited or hypoxic microenvironments during fungal pathogenesis. The implications of these in vivo hypoxic microenvironments for fungal metabolism and pathogenesis are discussed with an aim toward understanding the potential impact of hypoxia on invasive fungal infection outcomes.     

To Burst or Not to Burst?

It is well known that some neurons tend to fire packets of action potentials followed by periods of quiescence (bursts) while others within the same stage of sensory processing fire in a tonic manner. However, the respective computational advantages of bursting and tonic neurons for encoding time varying signals largely remain a mystery. Weakly electric fish use cutaneous electroreceptors to convey information about sensory stimuli and it has been shown that some electroreceptors exhibit bursting dynamics while others do not. In this study, we compare the neural coding capabilities of tonically firing and bursting electroreceptor model neurons using information theoretic measures. We find that both bursting and tonically firing model neurons efficiently transmit information about the stimulus. However, the decoding mechanisms that must be used for each differ greatly: a non-linear decoder would be required to extract all the available information transmitted by the bursting model neuron whereas a linear one might suffice for the tonically firing model neuron. Further investigations using stimulus reconstruction techniques reveal that, unlike the tonically firing model neuron, the bursting model neuron does not encode the detailed time course of the stimulus. A novel measure of feature detection reveals that the bursting neuron signals certain stimulus features. Finally, we show that feature extraction and stimulus estimation are mutually exclusive computations occurring in bursting and tonically firing model neurons, respectively. Our results therefore suggest that stimulus estimation and feature extraction might be parallel computations in certain sensory systems rather than being sequential as has been previously proposed.     

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.