What can we learn by studying enzymes in non-aqueous media?

What is the role of water in enzyme structure and function? One approach to answers should come from studies in which the amount of water present is a variable. In the absence of bulk liquid water, effective monitoring of enzyme action requires an alternative fluid medium through which substrates and products may be transported. The past 20 years have seen quite extensive study of enzyme behaviour when reactants are transferred via a bulk phase that is an organic liquid, a supercritical fluid or a gas. Some lipases, at least, remain highly active with only a few, if any, residual water molecules. Many enzymes seem to require larger amounts of water, but still not a liquid water phase. There are hysteresis effects on both the amount of bound water and the observed catalytic activity. Increasing hydration promotes mobility of the enzyme molecule, as revealed by various techniques, and there are correlations with catalytic activity. There are other plausible roles for hydration, such as opening up proton conduction pathways.     

What can we learn from Daphnia filtering screens?

The relative filtering setae length (RFSL the length of filteringsetae on the third pair of thoracic limbs expressed as a percent of carapace length) was determined in three developmentalcategories of a reservoir population of Daphnia galeata andits relationship to phytoplankton fluctuation. RFSL of adultfemales immediately after moulting reflects the current foodconditions in the reservoir (higher RFSL at lower food level,and vice versa), whereas RFSL of adult females close to moultingreflects the food conditions several days or weeks ago. RFSLof juvenile animals reacts the most quickly to changing foodconditions, provided the temperature allows frequent moulting.Higher RFSL can also indicate poor-quality food for daphnids,in situations when food quantitative parameters (such as chlorophylla) show high values.     

Vision for navigation: What can we learn from ants?

The visual systems of all animals are used to provide information that can guide behaviour. In some cases insects demonstrate particularly impressive visually-guided behaviour and then we might reasonably ask how the low-resolution vision and limited neural resources of insects are tuned to particular behavioural strategies. Such questions are of interest to both biologists and to engineers seeking to emulate insect-level performance with lightweight hardware. One behaviour that insects share with many animals is the use of learnt visual information for navigation. Desert ants, in particular, are expert visual navigators. Across their foraging life, ants can learn long idiosyncratic foraging routes. What's more, these routes are learnt quickly and the visual cues that define them can be implemented for guidance independently of other social or personal information. Here we review the style of visual navigation in solitary foraging ants and consider the physiological mechanisms that underpin it. Our perspective is to consider that robust navigation comes from the optimal interaction between behavioural strategy, visual mechanisms and neural hardware. We consider each of these in turn, highlighting the value of ant-like mechanisms in biomimetic endeavours.     

Antiviral strategies: What can we learn from natural reservoirs?

Viruses cause many severe diseases in both plants and animals, urging us to explore new antiviral strategies. In their natural reservoirs, viruses live and replicate while causing mild or no symptoms. Some animals, such as bats, are the predicted natural reservoir of multiple viruses, indicating that they possess broad-spectrum antiviral capabilities. Mechanisms of host defenses against viruses are generally studied independently in plants and animals. In this article, we speculate that some antiviral strategies of natural reservoirs are conserved between kingdoms. To verify this hypothesis, we created null mutants of 10-formyltetrahydrofolate synthetase (AtTHFS), an Arabidopsis thaliana homologue of methylenetetrahydrofolate dehydrogenase, cyclohydrolase and formyltetrahydrofolate synthetase 1 (MTHFD1), which encodes a positive regulator of viral replication in bats. We found that disruption of AtTHFS enhanced plant resistance to three different types of plant viruses, including the tomato spotted wilt virus (TSWV), the cucumber mosaic virus (CMV) and the beet severe curly top virus (BSCTV). These results demonstrate a novel antiviral strategy for plant breeding. We further discuss the approaches used to identify and study natural reservoirs of plant viruses, especially those hosting many viruses, and highlight the possibility of discovering new antiviral strategies from them for plant molecular breeding and antiviral therapy.     

Immunity to vacuolar pathogens: What can we learn from Legionella?

Intracellular pathogens can manipulate host cellular pathways to create specialized organelles. These pathogen-modified vacuoles permit the survival and replication of bacterial and protozoan microorganisms inside of the host cell. By establishing an atypical organelle, intracellular pathogens present unique challenges to the host immune system. To understand pathogenesis, it is important to not only investigate how these organisms create unique subcellular compartments, but to also determine how mammalian immune systems have evolved to detect and respond to pathogens sequestered in specialized vacuoles. Recent studies have identified genes in the respiratory pathogen Legionella pneumophila that are essential for establishing a unique endoplasmic reticulum-derived organelle inside of mammalian macrophages, making this pathogen an attractive model system for investigations on host immune responses that are specific for bacteria that establish vacuoles disconnected from the endocytic pathway. This review will focus on the host immune response to Legionella and highlight areas of Legionella research that should help elucidate host strategies to combat infections by intracellular pathogens.     

Keeping your vascular integrity: What can we learn from fish?

The cardiovascular system has the life-providing task of delivering oxygen and any flaw in this system can be life-threatening. This has encouraged extensive studies to elucidate the mechanisms behind cardiovascular development/homeostasis. The zebrafish has emerged as a formidable tool to speed up this quest, as illustrated in a recent issue of Nature Genetics.1 Baculovirus IAP repeat c2 (BIRC2), also termed cellular inhibitor of apoptosis (cIAP)-1, was found to specifically prevent endothelial cells (ECs, lining the inside of vessels) from going into suicide mode ('apoptosis') and so preserve vessel integrity. Here, we summarize the factors determining vascular integrity and elaborate on the suitability of the zebrafish to study this phenomenon.     

Towards Transgenic Primates: What can we learn from mouse genetics?

Considering the great physiological and behavioral similarities with humans, monkeys represent the ideal models not only for the study of complex cognitive behavior but also for the preclinical research and development of novel therapeutics for treating human diseases. Various powerful genetic technologies initially developed for making mouse models are being explored for generating transgenic primate models. We review the latest genetic engineering technologies and discuss the potentials and limitations for systematic production of transgenic primates. Supported by Funding from GRA, NIMH and NIA.     

What can we learn from tobacco and other Solanaceae about horizontal DNA transfer?

In eukaryotic organisms, horizontal gene transfer (HGT) is regarded as an important though infrequent source of reticulate evolution. Many confirmed instances of natural HGT involving multicellular eukaryotes come from flowering plants. This review intends to provide a synthesis of present knowledge regarding HGT in higher plants, with an emphasis on tobacco and other species in the Solanaceae family because there are numerous detailed reports concerning natural HGT events, involving various donors, in this family. Moreover, in-depth experimental studies using transgenic tobacco are of great importance for understanding this process. Valuable insights are offered concerning the mechanisms of HGT, the adaptive role and regulation of natural transgenes, and new routes for gene trafficking. With an increasing amount of data on HGT, a synthetic view is beginning to emerge.     

What can we learn about protein folding from Ising-like models?

Ising-like models have been remarkably successful in reproducing all the experimental data available on the equilibrium and kinetics of secondary structure formation in short peptides. Over the past two years, very similar models have been used to predict the folding of complete proteins, with encouraging results. Although Ising-like models are probably too simple to describe all aspects of protein folding, the results obtained so far indicate that they can play a critical role in the study of protein folding by bridging the gap between experiment and more detailed theoretical approaches.     

What can we learn about amphiphile-membrane interaction from model lipid membranes?

Surface-active amphiphiles find applications in a wide range of areas of industry such as agrochemicals, personal care, and pharmaceuticals. In many of these applications, interaction with cell membranes is a key factor for achieving their purpose. How do amphiphiles interact with lipid membranes? What are their bases for membrane specificity? Which biophysical properties of membranes are susceptible to modulation by amphiphilic membrane-effectors? What aspects of this interaction are important for performing their function? In our work on membrane biophysics over the years, questions like these have arisen and we now share some of our findings and discuss them in this review. This topic was approached focusing on the membrane properties and their alterations rather than on the amphiphile structure requirements for their interaction. Here, we do not aim to provide a comprehensive list of the modes of action of amphiphiles of biological interest but to help in understanding them.     

Archaea: what can we learn from their sequences?

Gene-by-gene and traditional biochemical approaches continue to reveal surprising molecular features in the archaeal domain. In addition, the complete sequencing of several archaeal genomes has further confirmed the phenotypic coherence of these micro-organisms at the molecular level. Nevertheless, the phylogeny of Archaea and the nature of the last universal common ancestor are still matters for debate.     

Structural analysis in nonsymbiotic hemoglobins: What can we learn from inner cavities?

Plants contain three classes of hemoglobins which are not associated with nitrogen fixing bacteria, and have been accordingly termed nonsymbiotic hemoglobins. The function of nonsymbiotic hemoglobins is as yet mostly unknown. A NO dioxygenase activity has been proposed and demonstrated for some of them in vitro. In this context, a sound molecular mechanism that relates the structure with the biological activity is crucial to suggest a given physiological role. Insight into such a mechanism is now facilitated by recent progress made in both experimental and computational techniques. These studies have highlighted a number of key structural features implicated in the function of nonsymbiotic hemoglobins. The bis-histidyl hexacoordination of the heme in both its ferric and ferrous states provides a powerful and general tool to modulate reactivity, protein dynamics, and shape of the cavities. In addition, the specific arrangement of distal cavity residues provides effective protection against autoxidation. Inspection of the static crystal structures available for both liganded and unliganded states seems unsufficient to explain the function of these proteins. Function appears to be intimately linked with protein flexibility, which influences the dynamical behavior of inner cavities, capable of delivering apolar reactants to the reaction site, and removing charged reaction products. In this mini review, we demonstrate how the integration of information derived from experimental assays and computational studies is valuable and can shed light into the linkage between structural plasticity of nonsymbiotic hemoglobins and their biological role.     

What can we learn from the optically recorded epicardial action potential?

Optical mapping using voltage-sensitive fluorescent dyes has become a major tool for studying excitation propagation in the heart. Computational and experimental studies have indicated that the optical upstroke morphology reflects the orientation of the subsurface excitation front. In a recent whole heart computational study performed by Bishop et al. (Bishop, M. J., B. Rodriguez, J. Eason, J. P. Whiteley, N. Trayanova, and D. J. Gavaghan. 2006. Synthesis of voltage-sensitive optical signals: application to panoramic optical mapping. Biophys. J. 90:2938-2945), an example was provided of two different directions of propagation having nevertheless very similar epicardial optical upstrokes. The goal of this comment is to clarify the interpretation of optical upstroke morphologies and reconcile the results obtained by Bishop et al. with previous computational and experimental studies.     

What can we learn from noncoding regions of similarity between genomes?

Background  

In addition to known protein-coding genes, large amounts of apparently non-coding sequence are conserved between the human and mouse genomes. It seems reasonable to assume that these conserved regions are more likely to contain functional elements than less-conserved portions of the genome.     

Bridging the explanatory gaps: What can we learn from a biological agency perspective?

We begin this article by delineating the explanatory gaps left by prevailing gene-focused approaches in our understanding of phenotype determination, inheritance, and the origin of novel traits. We aim not to diminish the value of these approaches but to highlight where their implementation, despite best efforts, has encountered persistent limitations. We then discuss how each of these explanatory gaps can be addressed by expanding research foci to take into account biological agency—the capacity of living systems at various levels to participate in their own development, maintenance, and function by regulating their structures and activities in response to conditions they encounter. Here we aim to define formally what agency and agents are and—just as importantly—what they are not, emphasizing that agency is an empirical property connoting neither intention nor consciousness. Lastly, we discuss how incorporating agency helps to bridge explanatory gaps left by conventional approaches, highlight scientific fields in which implicit agency approaches are already proving valuable, and assess the opportunities and challenges of more systematically incorporating biological agency into research programs.