Recent nuclear accidents have prompted renewed interest in the fitness consequences of low-dose radiation. Hiyama et al. provided information on such effects in the Japanese pale grass blue butterfly in a paper that has been viewed more than 300,000 times, prompting a barrage of criticism. These exchanges highlight the role of scrutiny in studies with potential effects on humans, but also raise questions about minimum requirements for demonstrating biological effects.
Interactions amongst genes, known as epistasis, are assumed to make a substantial contribution to the genetic variation in infectious disease susceptibility, but this claim is controversial. Here, we focus on the debate surrounding the evolutionary importance of interactions between resistance loci and argue that its role in explaining overall variance in disease outcomes may have been overestimated.
The morphology of mitochondrial networks is complex and highly varied, yet vital to cell function. The first step toward an integrative understanding of how mitochondrial morphology is generated and regulated is to define the interdependent geometrical features and their dynamics that together generate the morphology of a mitochondrial network within a cell. Distinct aspects of the size, shape, position, and dynamics of mitochondrial networks are described and examples of how these features depend on one another discussed.
During 30 years of research on human immunodeficiency virus (HIV), our knowledge of its cellular receptors - CD4, CCR5 and CXCR4 - has illuminated aspects of the pathogenesis of the acquired immune deficiency syndrome (AIDS). Studying how the HIV envelope glycoproteins interact with the receptors led to anti-retroviral drugs based on blocking the docking or fusion of virus to the host cell. Genetic polymorphisms of CCR5 determine resistance to HIV infection and the rate of progression to AIDS. Eliciting neutralizing antibodies to the sites of receptor interaction on HIV glycoproteins is a promising approach to HIV vaccine development.
AIDS; HIV; cell receptors; CD4; CCR5; CXCR4; Therapy
The fruit fly Drosophila has contributed significantly to our general understanding of the basic principles of signaling, cell and developmental biology, and neurobiology. However, answers to questions pertaining to energy metabolism have been so far mostly addressed in more complex model organisms such as mice. We review in this article recent studies that show how the genetic tractability and simplicity of Drosophila are being used to identify novel regulatory mechanisms at the organismal level, and to query the co-ordination between energy metabolism and other processes such as neurodegeneration, circadian rhythms, immunity, and tumor biology.
The clockwise rotation of cilia in the developing mammalian embryo drives a leftward flow of liquid; this genetically regulated biophysical force specifies left-right asymmetry of the mammalian body. How leftward flow is interpreted and information propagated to other tissues is the subject of debate. Four recent papers have shed fresh light on the possible mechanisms.
Logic-derived modeling has been used to map biological networks and to study arbitrary functional interactions, and fine-grained kinetic modeling can accurately predict the detailed behavior of well-characterized molecular systems; at present, however, neither approach comes close to unraveling the full complexity of a cell. The current data revolution offers significant promises and challenges to both approaches - and could bring them together as it has spurred the development of new methods and tools that may help to bridge the many gaps between data, models, and mechanistic understanding.
Have you used logic modeling in your research? It would not be surprising if many biologists would answer no to this hypothetical question. And it would not be true. In high school biology we already became familiar with cartoon diagrams that illustrate basic mechanisms of the molecular machinery operating inside cells. These are nothing else but simple logic models. If receptor and ligand are present, then receptor-ligand complexes form; if a receptor-ligand complex exists, then an enzyme gets activated; if the enzyme is active, then a second messenger is being produced; and so on. Such chains of causality are the essence of logic models (Figure 1a). Arbitrary events and mechanisms are abstracted; relationships are simplified and usually involve just two possible conditions and three possible consequences. The presence or absence of one or more molecule, activity, or function, [some icons in the cartoon] will determine whether another one of them will be produced (created, up-regulated, stimulated) [a 'positive' link] or destroyed (degraded, down-regulated, inhibited) [a 'negative' link], or be unaffected [there is no link]. The icons and links often do not follow a standardized format, but when we look at such a cartoon diagram, we believe that we 'understand' how the system works. Because our brain is easily able to process these relationships, these diagrams allow us to answer two fundamental types of questions related to the system: why (are certain things happening)? What if (we make some changes)?
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