Hfsp Journal最新文献

Rhythmic and sequential subdivision of the elongating vertebrate embryonic body axis into morphological somites is controlled by an oscillating multicellular genetic network termed the segmentation clock. This clock operates in the presomitic mesoderm (PSM), generating dynamic stripe patterns of oscillatory gene-expression across the field of PSM cells. How these spatial patterns, the clock's collective period, and the underlying cellular-level interactions are related is not understood. A theory encompassing temporal and spatial domains of local and collective aspects of the system is essential to tackle these questions. Our delayed coupling theory achieves this by representing the PSM as an array of phase oscillators, combining four key elements: a frequency profile of oscillators slowing across the PSM; coupling between neighboring oscillators; delay in coupling; and a moving boundary describing embryonic axis elongation. This theory predicts that the segmentation clock's collective period depends on delayed coupling. We derive an expression for pattern wavelength across the PSM and show how this can be used to fit dynamic wildtype gene-expression patterns, revealing the quantitative values of parameters controlling spatial and temporal organization of the oscillators in the system. Our theory can be used to analyze experimental perturbations, thereby identifying roles of genes involved in segmentation.

Intracellular Ca(2+) distribution and its dynamics are essential for various cellular functions. We show with single HeLa cells that a microscopic heat pulse induces Ca(2+) uptake into intracellular stores during heating and Ca(2+) release from them at the onset of recooling, and the overshoot of Ca(2+) release occurs above the critical value of a temperature change, which decreases from 1.5 to 0.2 degrees C on increasing the experimental temperature from 22 to 37 degrees C. This highly thermosensitive Ca(2+) dynamics is probably attributable to the altered balance between Ca(2+) uptake by endoplasmic reticulum Ca(2+)-ATPases and Ca(2+) release via inositol 1,4,5-trisphosphate receptors. These results suggest that Ca(2+) signaling is extremely sensitive to temperature changes, especially around body temperature, in cells expressing inositol 1,4,5-trisphosphate receptors.

Human conception, indeed fertilization in general, takes place in a fluid, but what role does fluid dynamics have during the subsequent development of an organism? It is becoming increasingly clear that the number of genes in the genome of a typical organism is not sufficient to specify the minutiae of all features of its ontogeny. Instead, genetics often acts as a choreographer, guiding development but leaving some aspects to be controlled by physical and chemical means. Fluids are ubiquitous in biological systems, so it is not surprising that fluid dynamics should play an important role in the physical and chemical processes shaping ontogeny. However, only in a few cases have the strands been teased apart to see exactly how fluid forces operate to guide development. Here, we review instances in which the hand of fluid dynamics in developmental biology is acknowledged, both in human development and within a wider biological context, together with some in which fluid dynamics is notable but whose workings have yet to be understood, and we provide a fluid dynamicist's perspective on possible avenues for future research.

Since the discovery of gene products oscillating during the formation of vertebral segments, much attention has been directed toward eluciating the molecular basis of the so-called segmentation clock. What research has told us is, that even in the most simple vertebrates, enormously complicated gene networks act in each cell to give rise to oscillations, and that cell-cell communication synchronizes these oscillations between neighboring cells. A number of theories have been proposed to explain both the initiation and maintenance of oscillations in a single cell and the synchronization of such oscillations between cells. We discuss these theories in this Commentary.

This paper extends previous work on the Darwinian evolutionary fitness effect of the fixation of deleterious mutations by incorporating compensatory mutations, which are mutations (deleterious by themselves) that ameliorate other deleterious mutations, thus reducing the genetic load of populations. Since having compensatory mutations essentially changes the distributional shapes of deleterious mutations, the effect of compensatory mutations is studied by comparing distributions of deleterious mutations without compensatory mutations to those with compensatory mutations. The effect of effective population size (N(e)), fitness distributional shape, and mutation rate on population fitness reduction is studied. Results indicate that, first, the smaller a population's N(e), the larger the effect of compensatory mutations on fitness recovery, and the compensatory effect increases sharply with decreasing N(e). Second, the larger the squared coefficient of variation in the fitness effect of deleterious mutations, the larger the effect of compensatory mutations. Third, for fixed N(e), the higher the rate of deleterious mutations, the more effective compensatory mutation is in fitness recovery, and this effect is more pronounced for smaller N(e).

Computational simulations of the electrodynamics of cardiac fibrillation yield a great deal of useful data and provide a framework for theoretical explanations of heart behavior. Extending the application of these mathematical models to defibrillation studies requires that a simulation should sustain fibrillation without defibrillation intervention. In accordance with the critical mass hypothesis, the simulated tissue should be of a large enough size. The choice of biperiodic boundary conditions sustains fibrillation for a longer duration than no-flux boundary conditions for a given area, and so is commonly invoked. Here, we show how this leads to a boundary condition artifact that may complicate the analysis of defibrillation efficacy; we implement an alternative coordinate scheme that utilizes spherical shell topology and mitigates singularities in the Laplacian found with the usual spherical curvilinear coordinate system.

This short review presents a qualitative introduction to the hydrodynamic theory of active polar gels and its applications to the mechanics of the cytoskeleton. Active polar gels are viscoelastic materials formed by polar filaments maintained in a nonequilibrium state by constant consumption of energy. In the cytoskeleton of eukaryotic cells, actin filaments are treadmilling and form a viscoelastic gel interacting with myosin molecular motors driven by the hydrolysis of adenosine triphosphate; one can thus consider the actomyosin cytoskeleton as an active polar gel. The hydrodynamic description is generic as it only relies on symmetry arguments. We first use the hydrodynamic approach to discuss the spontaneous generation of flow in an active polar film. Then we give two examples of applications to lamellipodium motility and to instabilities of cortical actin.

Gastrulation is a critical stage in the development of all vertebrates. During gastrulation mesendoderm cells move inside the embryo to form the gut, muscles, and skeleton. In amniotes the mesendoderm cells move inside the embryo through a structure known as the primitive streak, extending from the posterior pole anterior through the midline of the embryo. Primitive streak formation involves large scale cell flows of a layer of highly polarized epithelial epiblast cells. The epiblast is separated from a lower layer of hypoblast cells through a well developed basal lamina. Recent experiments in which in vivo extracellular matrix dynamics was followed via labeling with fibronectin specific fluorescent antibodies and time-lapse microscopy have suggested that extracellular matrix dynamics essentially coincides with the observed epiblast cell displacements (Zamir et al., 2008, PLoS Biol 6, e247). These observations raise the important question of who moves whom and where do cells derive traction. We discuss these matters and their implications for our understanding of the mechanisms underlying cell flows during primitive streak formation in the chick embryo.

The nuclear pore supports molecular communication between cytoplasm and nucleus in eukaryotic cells. Selective transport of proteins is mediated by soluble receptors, whose regulation by the small GTPase Ran leads to cargo accumulation in, or depletion from, the nucleus, i.e., nuclear import or nuclear export. We consider the operation of this transport system by a combined analytical and experimental approach. Provocative predictions of a simple model were tested using cell-free nuclei reconstituted in Xenopus egg extract, a system well suited to quantitative studies. We found that accumulation capacity is limited, so that introduction of one import cargo leads to egress of another. Clearly, the pore per se does not determine transport directionality. Moreover, different cargo reach a similar ratio of nuclear to cytoplasmic concentration in steady-state. The model shows that this ratio should in fact be independent of the receptor-cargo affinity, though kinetics may be strongly influenced. Numerical conservation of the system components highlights a conflict between the observations and the popular concept of transport cycles. We suggest that chemical partitioning provides a framework to understand the capacity to generate concentration gradients by equilibration of the receptor-cargo intermediary.

Our visual system can operate at fascinating speeds. Psychophysical experiments teach us that the processing of complex natural images and visual object recognition require a mere split second. Even in everyday life, our gaze seldom rests for long on any particular spot of the visual scene before a sudden movement of the eyes or the head shifts it to a new location. These observations challenge our understanding of how neurons in the visual system of the brain represent, process, and transmit the relevant visual information quickly enough. This article argues that the speed of visual processing provides an adjuvant framework for studying the neural code in the visual system. In the retina, which constitutes the first stage of visual processing, recent experiments have highlighted response features that allow for particularly rapid information transmission. This sets the stage for discussing some of the fundamental questions in the research of neural coding. How do downstream brain regions read out signals from the retina and combine them with intrinsic signals that accompany eye movements? And, how do the neural response features ultimately affect perception and behavior?