Cells on the run: shear-regulated integrin activation in leukocyte rolling and arrest on endothelial cells

The arrest of rolling leukocytes on various target vascular beds is mediated by specialized leukocyte integrins and their endothelial immunoglobulin superfamily (IgSF) ligands. These integrins are kept in largely inactive states and undergo in situ activation upon leukocyte-endothelial contact by both biochemical and mechanical signals from flow-derived shear forces. In vivo and in vitro studies suggest that leukocyte integrin activation involves conformational alterations through inside-out signaling followed by ligand-induced rearrangements accelerated by external forces. This activation process takes place within fractions of seconds by in situ signals transduced to the rolling leukocyte as it encounters specialized endothelial-displayed chemoattractants, collectively termed arrest chemokines. In neutrophils, selectin rolling engagements trigger intermediate affinity integrins to support reversible adhesions before chemokine-triggered arrest. Different leukocyte subsets appear to use different modalities of integrin activation during rolling and arrest at distinct endothelial sites.     

It depends on the hinge: a structure-functional analysis of galectin-8, a tandem-repeat type lectin

Galectin-8, a member of the galectin family of mammalian lectins, is made of two carbohydrate-recognition domains (CRDs), joined by a "hinge" region. Ligation of integrins by galectin-8 induces a distinct cytoskeletal organization, associated with activation of the extracellular-regulated kinase (ERK) and phosphatidylinositol 3-kinase signaling cascades. We show that these properties of galectin-8 are mediated by the concerted action of its two CRDs and involve both protein-sugar and protein-protein interactions. Accordingly, the isolated N- or C-CRD domains of galectin-8 or galectin-8 mutated at selected residues implicated in sugar binding (E251Q; W85Y, W248Y, W[85,248]Y) exhibited reduced sugar binding, which was accompanied by severe impairment in the capacity of these mutants to promote the adhesive, spreading, and signaling functions of galectin-8. Other mutations that did not impair sugar binding (e.g. E88Q) still impeded the signaling and cell-adherence functions of galectin-8. Deletion of the "hinge" region similarly impaired the biological effects of galectin-8. These results provide evidence that cooperative interactions between the two CRDs and the "hinge" domain are required for the proper functioning of galectin-8.     

How much the eye tells the brain

In the classic "What the frog's eye tells the frog's brain," Lettvin and colleagues showed that different types of retinal ganglion cell send specific kinds of information. For example, one type responds best to a dark, convex form moving centripetally (a fly). Here we consider a complementary question: how much information does the retina send and how is it apportioned among different cell types? Recording from guinea pig retina on a multi-electrode array and presenting various types of motion in natural scenes, we measured information rates for seven types of ganglion cell. Mean rates varied across cell types (6-13 bits . s(-1)) more than across stimuli. Sluggish cells transmitted information at lower rates than brisk cells, but because of trade-offs between noise and temporal correlation, all types had the same coding efficiency. Calculating the proportions of each cell type from receptive field size and coverage factor, we conclude (assuming independence) that the approximately 10(5) ganglion cells transmit on the order of 875,000 bits . s(-1). Because sluggish cells are equally efficient but more numerous, they account for most of the information. With approximately 10(6) ganglion cells, the human retina would transmit data at roughly the rate of an Ethernet connection.     

Predicting Carriers of Ongoing Selective Sweeps without Knowledge of the Favored Allele

Methods for detecting the genomic signatures of natural selection have been heavily studied, and they have been successful in identifying many selective sweeps. For most of these sweeps, the favored allele remains unknown, making it difficult to distinguish carriers of the sweep from non-carriers. In an ongoing selective sweep, carriers of the favored allele are likely to contain a future most recent common ancestor. Therefore, identifying them may prove useful in predicting the evolutionary trajectory—for example, in contexts involving drug-resistant pathogen strains or cancer subclones. The main contribution of this paper is the development and analysis of a new statistic, the Haplotype Allele Frequency (HAF) score. The HAF score, assigned to individual haplotypes in a sample, naturally captures many of the properties shared by haplotypes carrying a favored allele. We provide a theoretical framework for computing expected HAF scores under different evolutionary scenarios, and we validate the theoretical predictions with simulations. As an application of HAF score computations, we develop an algorithm (PreCIOSS: Predicting Carriers of Ongoing Selective Sweeps) to identify carriers of the favored allele in selective sweeps, and we demonstrate its power on simulations of both hard and soft sweeps, as well as on data from well-known sweeps in human populations.     

Light asymmetry explains the effect of nutrient enrichment on grassland diversity

One of the most ubiquitous patterns in plant ecology is species loss following nutrient enrichment. A common explanation for this universal pattern is an increase in the size asymmetry of light partitioning (the degree to which large plants receive more light per unit biomass than smaller plants), which accelerates the rates of competitive exclusions. This ‘light asymmetry hypothesis’ has been confirmed by mathematical models, but has never been tested in natural communities due to the lack of appropriate methodology for measuring the size asymmetry of light partitioning in natural communities. Here, we use a novel approach for quantifying the asymmetry of light competition which is based on measurements of the vertical distribution of light below the canopy. Using our approach, we demonstrate that an increase in light asymmetry is the main mechanism behind the negative effect of nutrient enrichment on species richness. Our results provide a possible explanation for one of the main sources of contemporary species loss in terrestrial plant communities.